{"gene":"PODXL","run_date":"2026-06-10T06:43:35","timeline":{"discoveries":[{"year":2003,"finding":"The embryonal carcinoma tumor antigen gp200 (also known as GCTM-2) was identified as podocalyxin (PODXL) by protein sequencing of gp200 peptides and reactivity with two distinct anti-podocalyxin monoclonal antibodies, establishing PODXL as the first reported podocalyxin expressed on malignant cells.","method":"Protein peptide sequencing and monoclonal antibody reactivity assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — peptide sequencing plus two orthogonal antibody validations in a single study confirm molecular identity","pmids":["12504081"],"is_preprint":false},{"year":2008,"finding":"PODXL (podocalyxin-like protein) is selectively expressed on early progenitor mesenchymal stem cells (MSCs); RNA interference knockdown of PODXL caused cell aggregation, demonstrating PODXL is required to prevent aggregation in these progenitor cells. PODXL(hi) MSCs showed greater clonogenicity, more efficient differentiation, and enhanced migration to infarcted heart after intravenous infusion compared to PODXL(lo) cells.","method":"FACS sorting, RNAi knockdown with phenotypic readout (aggregation), in vivo intravenous infusion with tissue recovery","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi loss-of-function with defined cellular phenotype (aggregation), complemented by in vivo trafficking assay, single lab","pmids":["18818395"],"is_preprint":false},{"year":2012,"finding":"miR-199b-5p directly targets PODXL in acute myeloid leukemia (AML); 3'UTR-luciferase assays and mimic transfections established PODXL as a direct post-transcriptional target. Overexpression of miR-199b-5p in K562 cells caused significant decrease in collagen IV-induced migration, linking PODXL expression to cell migration.","method":"3'UTR-luciferase reporter assay, miRNA mimic transfection, cell migration assay","journal":"American journal of hematology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — 3'UTR luciferase plus functional migration assay, single lab, two orthogonal methods","pmids":["22374871"],"is_preprint":false},{"year":2016,"finding":"miR-5100 directly binds to the 3'UTR of PODXL and post-transcriptionally represses its expression in pancreatic cancer cells; PODXL silencing diminished cell migration and invasion, demonstrating PODXL promotes metastatic properties in pancreatic cancer.","method":"3'UTR reporter assay, miRNA overexpression, siRNA knockdown with migration and invasion assays","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — 3'UTR reporter plus loss-of-function phenotypic assays (migration, invasion), single lab, multiple orthogonal methods","pmids":["26892887"],"is_preprint":false},{"year":2016,"finding":"PODXL is a carrier protein for pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81, GCTM2, GP200, mAb84) in human pluripotent stem cells. PODXL is activated by KLF4 during reprogramming. An antibody to the universal PODXL epitope 3D3 causes massive necrosis and apoptosis of human pluripotent stem cells (hPSCs), demonstrating PODXL surface expression mediates cytotoxic antibody sensitivity.","method":"Flow cytometry, antibody-mediated cytotoxicity assay, reprogramming with KLF4 overexpression","journal":"Stem cells and development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional antibody cytotoxicity assay plus reprogramming experiments, single lab, multiple methods","pmids":["26886504"],"is_preprint":false},{"year":2016,"finding":"A homozygous frameshift mutation (c.89_90insGTCGCCCC) in exon 1 of PODXL, resulting in loss of protein, segregated with autosomal-recessive juvenile Parkinsonism in a family. Functional validation in differentiated PC12 cells showed significant differences in neurite branching and length between wild-type and mutant PODXL constructs, establishing a role for PODXL in neuronal morphology.","method":"Whole-exome sequencing, Sanger sequencing for segregation, functional assay in PC12 cells (neurite branching/length measurement)","journal":"Journal of medical genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function genetic variant with functional PC12 cell validation, single lab, two orthogonal approaches","pmids":["26864383"],"is_preprint":false},{"year":2019,"finding":"PODXL1 binds directly to C5aR (complement component 5a receptor), stabilizing C5aR protein and recruiting it to the cancer cell plasma membrane to receive C5a; PODXL1 knockout in pancreatic ductal adenocarcinoma (PDAC) cells abolished their metastatic property in a liver metastatic mouse model. C5a stimulation of PODXL1-expressing cells triggered epithelial-mesenchymal transition (EMT), demonstrating PODXL1 promotes PDAC metastasis via the C5aR/C5a axis.","method":"Co-immunoprecipitation/direct binding assay, PODXL1 knockout (in vitro and in vivo), liver metastasis mouse model, EMT assay, anti-C5a neutralizing antibody treatment","journal":"Neoplasia (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal binding assay, in vitro functional assays, and in vivo knockout metastasis model with antibody validation, multiple orthogonal methods in single study","pmids":["31759250"],"is_preprint":false},{"year":2021,"finding":"TCF3 transcription factor directly regulates PODXL transcription in human spermatogonial stem cells (SSCs), as demonstrated by ChIP assay; PODXL silencing compromised stem cell activity of SSCs, establishing PODXL as a downstream effector of TCF3 in maintaining SSC proliferation and suppressing apoptosis.","method":"RNA sequencing, chromatin immunoprecipitation (ChIP), siRNA knockdown with proliferation/apoptosis assays","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP assay confirming direct transcriptional regulation plus loss-of-function phenotype, single lab, two orthogonal methods","pmids":["34422820"],"is_preprint":false},{"year":2022,"finding":"miR-34c-5p (delivered via platelet-derived extracellular vesicles) targets PODXL by binding to its 3'UTR; depletion of PODXL by miR-34c-5p blocked the P38 MAPK signaling pathway, thereby attenuating ox-LDL-induced inflammation (IL-1β, IL-6, TNF-α) in human coronary artery endothelial cells.","method":"3'UTR luciferase assay, gain- and loss-of-function experiments, P38 MAPK pathway analysis, in vitro cell model and ApoE knockout mouse model","journal":"Nutrition, metabolism, and cardiovascular diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — 3'UTR reporter plus pathway inhibition assays and in vivo validation, single lab, multiple methods","pmids":["36096977"],"is_preprint":false}],"current_model":"PODXL (podocalyxin-like protein) is a sialomucin-family cell surface glycoprotein that carries pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81) in stem cells, prevents cell aggregation in MSC progenitors, promotes cancer cell migration and invasion by physically interacting with C5aR to stabilize it at the plasma membrane and mediate C5a-induced EMT, and contributes to neuronal morphology; its expression is post-transcriptionally regulated by multiple miRNAs (miR-199b-5p, miR-5100, miR-34c-5p, miR-1301-3p, miR-361-3p) and transcriptionally by TCF3, with downstream signaling through the P38 MAPK pathway."},"narrative":{"mechanistic_narrative":"PODXL (podocalyxin-like protein) is a cell-surface sialomucin that controls cell adhesion, migration, and surface receptor presentation across stem cell, cancer, and neuronal contexts [PMID:18818395, PMID:31759250]. In pluripotent and progenitor cells it functions as the carrier of pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81, GCTM-2/gp200), and its abundance is set during reprogramming by KLF4; antibody engagement of its surface epitope is acutely cytotoxic, marking it as a defining surface determinant of these cells [PMID:12504081, PMID:26886504]. On mesenchymal stem cell progenitors PODXL acts as an anti-adhesive that prevents cell aggregation, with high-PODXL cells showing greater clonogenicity and migratory capacity [PMID:18818395]. In cancer, PODXL drives migration, invasion, and metastasis: it binds directly to the complement receptor C5aR, stabilizing it and recruiting it to the plasma membrane so that C5a stimulation triggers epithelial-mesenchymal transition, and its loss abolishes metastatic capacity in vivo [PMID:31759250]. PODXL expression is constrained post-transcriptionally by multiple 3'UTR-targeting miRNAs and activated transcriptionally by TCF3, with downstream inflammatory signaling proceeding through the P38 MAPK pathway [PMID:26892887, PMID:34422820, PMID:36096977]. A homozygous loss-of-function frameshift mutation in PODXL segregates with autosomal-recessive juvenile Parkinsonism, and mutant PODXL alters neurite branching and length, linking the protein to neuronal morphology [PMID:26864383].","teleology":[{"year":2003,"claim":"Established the molecular identity of a malignant-cell tumor antigen, resolving that the embryonal carcinoma antigen gp200/GCTM-2 is podocalyxin and that PODXL is expressed on malignant cells.","evidence":"Protein peptide sequencing of gp200 with reactivity against two anti-podocalyxin monoclonal antibodies","pmids":["12504081"],"confidence":"Medium","gaps":["Did not define a function for PODXL on malignant cells","No mechanism linking the antigen to a signaling or adhesion role"]},{"year":2008,"claim":"Defined an anti-adhesive cellular function for PODXL in progenitor cells, showing it prevents aggregation and marks cells with superior clonogenic and migratory behavior.","evidence":"FACS sorting, RNAi knockdown with aggregation readout, and in vivo intravenous infusion/tissue recovery in MSCs","pmids":["18818395"],"confidence":"Medium","gaps":["Molecular basis of the anti-adhesive effect not resolved","Surface partners mediating aggregation prevention not identified"]},{"year":2012,"claim":"Connected PODXL abundance to migratory phenotype and identified the first miRNA control point, establishing PODXL as a direct 3'UTR target of miR-199b-5p in AML.","evidence":"3'UTR-luciferase reporter, miRNA mimic transfection, and collagen IV-induced migration assay in K562 cells","pmids":["22374871"],"confidence":"Medium","gaps":["Downstream effectors linking PODXL to migration not defined","Single cell-line context"]},{"year":2016,"claim":"Cemented PODXL as the carrier of pluripotency surface epitopes and a reprogramming-regulated, cytotoxicity-defining surface marker of human pluripotent stem cells.","evidence":"Flow cytometry, antibody-mediated cytotoxicity assay, and KLF4-driven reprogramming","pmids":["26886504"],"confidence":"Medium","gaps":["Mechanism by which surface PODXL engagement triggers necrosis/apoptosis not defined","Glycosylation enzymes generating the epitopes not identified"]},{"year":2016,"claim":"Extended the miRNA-PODXL regulatory axis to solid tumors, showing miR-5100 represses PODXL and that PODXL is required for migration and invasion in pancreatic cancer.","evidence":"3'UTR reporter, miRNA overexpression, and siRNA knockdown with migration/invasion assays in pancreatic cancer cells","pmids":["26892887"],"confidence":"Medium","gaps":["Signaling mechanism downstream of PODXL not addressed","In vivo metastasis not tested"]},{"year":2016,"claim":"Linked PODXL loss to human disease and a neuronal phenotype, implicating PODXL in neurite morphology through a familial Parkinsonism mutation.","evidence":"Whole-exome and Sanger sequencing for segregation plus neurite branching/length assay in PC12 cells","pmids":["26864383"],"confidence":"Medium","gaps":["Mechanism by which PODXL shapes neurite morphology unknown","Single family; neuronal signaling partners not identified"]},{"year":2019,"claim":"Provided the most direct mechanism for PODXL-driven metastasis, showing it binds and stabilizes C5aR at the plasma membrane to enable C5a-induced EMT.","evidence":"Co-immunoprecipitation/direct binding, PODXL1 knockout in vitro and in a liver metastasis mouse model, EMT assays, and anti-C5a neutralizing antibody","pmids":["31759250"],"confidence":"High","gaps":["Structural basis of the PODXL1-C5aR interaction not resolved","Whether this axis operates in non-PDAC tumors not established"]},{"year":2021,"claim":"Identified upstream transcriptional control of PODXL, establishing it as a direct TCF3 target required for spermatogonial stem cell maintenance.","evidence":"RNA-seq, ChIP, and siRNA knockdown with proliferation/apoptosis assays in human SSCs","pmids":["34422820"],"confidence":"Medium","gaps":["Mechanism by which PODXL sustains SSC proliferation not defined","Surface signaling output in SSCs not characterized"]},{"year":2022,"claim":"Placed PODXL within an inflammatory signaling cascade, showing miR-34c-5p repression of PODXL blocks P38 MAPK and attenuates endothelial inflammation.","evidence":"3'UTR luciferase, gain/loss-of-function, P38 MAPK pathway analysis, and ApoE-knockout mouse model","pmids":["36096977"],"confidence":"Medium","gaps":["How PODXL couples to P38 MAPK activation not defined","Direct membrane partners in endothelial cells not identified"]},{"year":null,"claim":"How PODXL's extracellular sialomucin/anti-adhesive properties are mechanistically integrated with its receptor-stabilizing and intracellular signaling functions across these diverse cell types remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of PODXL or its receptor complexes","Cytoplasmic adaptors transducing PODXL signals not defined in the corpus","Glycan-epitope biosynthetic machinery not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[1]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[6]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[4,6]}],"pathway":[{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[6,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[6,8]}],"complexes":[],"partners":["C5AR1","KLF4","TCF3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O00592","full_name":"Podocalyxin","aliases":["GCTM-2 antigen","Gp200","Podocalyxin-like protein 1","PC","PCLP-1"],"length_aa":558,"mass_kda":58.6,"function":"Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells","subcellular_location":"Apical cell membrane; Cell projection, lamellipodium; Cell projection, filopodium; Cell projection, ruffle; Cell projection, microvillus; Membrane raft; Membrane","url":"https://www.uniprot.org/uniprotkb/O00592/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PODXL","classification":"Not Classified","n_dependent_lines":8,"n_total_lines":1208,"dependency_fraction":0.006622516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"SLC9A3R2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/PODXL","total_profiled":1310},"omim":[{"mim_id":"616627","title":"PODOCALYXIN-LIKE 2; PODXL2","url":"https://www.omim.org/entry/616627"},{"mim_id":"606553","title":"SOLUTE CARRIER FAMILY 9, MEMBER 3, REGULATOR 2; SLC9A3R2","url":"https://www.omim.org/entry/606553"},{"mim_id":"602632","title":"PODOCALYXIN-LIKE; PODXL","url":"https://www.omim.org/entry/602632"},{"mim_id":"600116","title":"PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE; PARK2","url":"https://www.omim.org/entry/600116"},{"mim_id":"123900","title":"EZRIN; EZR","url":"https://www.omim.org/entry/123900"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Endoplasmic reticulum","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"kidney","ntpm":130.6}],"url":"https://www.proteinatlas.org/search/PODXL"},"hgnc":{"alias_symbol":["PCLP","Gp200","PC","PODXL1","PDX","gp135"],"prev_symbol":[]},"alphafold":{"accession":"O00592","domains":[{"cath_id":"-","chopping":"341-348_356-419","consensus_level":"high","plddt":80.0483,"start":341,"end":419},{"cath_id":"-","chopping":"420-451","consensus_level":"medium","plddt":81.9425,"start":420,"end":451},{"cath_id":"1.20.5","chopping":"460-498","consensus_level":"medium","plddt":83.2136,"start":460,"end":498}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00592","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00592-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00592-F1-predicted_aligned_error_v6.png","plddt_mean":52.91},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PODXL","jax_strain_url":"https://www.jax.org/strain/search?query=PODXL"},"sequence":{"accession":"O00592","fasta_url":"https://rest.uniprot.org/uniprotkb/O00592.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00592/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00592"}},"corpus_meta":[{"pmid":"8631275","id":"PMC_8631275","title":"PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.","date":"1996","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8631275","citation_count":1294,"is_preprint":false},{"pmid":"22570331","id":"PMC_22570331","title":"Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes.","date":"2012","source":"Molecular endocrinology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/22570331","citation_count":236,"is_preprint":false},{"pmid":"9315659","id":"PMC_9315659","title":"Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene.","date":"1997","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9315659","citation_count":223,"is_preprint":false},{"pmid":"31412684","id":"PMC_31412684","title":"Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models.","date":"2019","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/31412684","citation_count":217,"is_preprint":false},{"pmid":"28025748","id":"PMC_28025748","title":"Patient-derived xenograft (PDX) models in basic and translational breast cancer research.","date":"2016","source":"Cancer metastasis reviews","url":"https://pubmed.ncbi.nlm.nih.gov/28025748","citation_count":207,"is_preprint":false},{"pmid":"11692168","id":"PMC_11692168","title":"Pancreatic duodenal homeobox-1, PDX-1, a major regulator of beta cell identity and function.","date":"2001","source":"Diabetologia","url":"https://pubmed.ncbi.nlm.nih.gov/11692168","citation_count":197,"is_preprint":false},{"pmid":"12829640","id":"PMC_12829640","title":"PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells.","date":"2003","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/12829640","citation_count":183,"is_preprint":false},{"pmid":"18818395","id":"PMC_18818395","title":"The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice.","date":"2008","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/18818395","citation_count":148,"is_preprint":false},{"pmid":"17938503","id":"PMC_17938503","title":"PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function.","date":"2007","source":"Endocrine journal","url":"https://pubmed.ncbi.nlm.nih.gov/17938503","citation_count":127,"is_preprint":false},{"pmid":"9492081","id":"PMC_9492081","title":"Conservation of PDX-1 structure, function, and expression in zebrafish.","date":"1998","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/9492081","citation_count":118,"is_preprint":false},{"pmid":"32990680","id":"PMC_32990680","title":"PDX-derived organoids model in vivo drug response and secrete biomarkers.","date":"2020","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/32990680","citation_count":101,"is_preprint":false},{"pmid":"15028942","id":"PMC_15028942","title":"PDX-1 and the pancreas.","date":"2004","source":"Pancreas","url":"https://pubmed.ncbi.nlm.nih.gov/15028942","citation_count":90,"is_preprint":false},{"pmid":"31479514","id":"PMC_31479514","title":"The fidelity of cancer cells in PDX models: Characteristics, mechanism and clinical significance.","date":"2019","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31479514","citation_count":90,"is_preprint":false},{"pmid":"15153417","id":"PMC_15153417","title":"Transcription factors in islet development and physiology: role of PDX-1 in beta-cell function.","date":"2004","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/15153417","citation_count":85,"is_preprint":false},{"pmid":"12504081","id":"PMC_12504081","title":"Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin.","date":"2003","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/12504081","citation_count":74,"is_preprint":false},{"pmid":"19755420","id":"PMC_19755420","title":"Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19755420","citation_count":71,"is_preprint":false},{"pmid":"10588826","id":"PMC_10588826","title":"PDX-1 and Msx-2 expression in the regenerating and developing pancreas.","date":"1999","source":"The Journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/10588826","citation_count":69,"is_preprint":false},{"pmid":"31585941","id":"PMC_31585941","title":"A Comprehensive PDX Gastric Cancer Collection Captures Cancer Cell-Intrinsic Transcriptional MSI Traits.","date":"2019","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/31585941","citation_count":67,"is_preprint":false},{"pmid":"26783960","id":"PMC_26783960","title":"Patient-derived xenograft (PDX) tumors increase growth rate with time.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/26783960","citation_count":67,"is_preprint":false},{"pmid":"15652518","id":"PMC_15652518","title":"Enhanced expression of PDX-1 and Ngn3 by exendin-4 during beta cell regeneration in STZ-treated mice.","date":"2005","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15652518","citation_count":67,"is_preprint":false},{"pmid":"17192469","id":"PMC_17192469","title":"Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1 and NKX6.1 in INS-1 cells.","date":"2007","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/17192469","citation_count":61,"is_preprint":false},{"pmid":"17383157","id":"PMC_17383157","title":"Ectopic PDX-1 expression in liver ameliorates type 1 diabetes.","date":"2007","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/17383157","citation_count":57,"is_preprint":false},{"pmid":"15896300","id":"PMC_15896300","title":"Mechanism of PDX-1 protein transduction.","date":"2005","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15896300","citation_count":57,"is_preprint":false},{"pmid":"12551916","id":"PMC_12551916","title":"The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12551916","citation_count":54,"is_preprint":false},{"pmid":"29463559","id":"PMC_29463559","title":"Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers.","date":"2018","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/29463559","citation_count":52,"is_preprint":false},{"pmid":"30912026","id":"PMC_30912026","title":"Creation of PDX-Bearing Humanized Mice to Study Immuno-oncology.","date":"2019","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/30912026","citation_count":51,"is_preprint":false},{"pmid":"28442585","id":"PMC_28442585","title":"Next-Generation Sequencing Analysis and Algorithms for PDX and CDX Models.","date":"2017","source":"Molecular cancer research : MCR","url":"https://pubmed.ncbi.nlm.nih.gov/28442585","citation_count":45,"is_preprint":false},{"pmid":"17627512","id":"PMC_17627512","title":"Crucial role of PDX-1 in pancreas development, beta-cell differentiation, and induction of surrogate beta-cells.","date":"2007","source":"Current medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17627512","citation_count":45,"is_preprint":false},{"pmid":"36551213","id":"PMC_36551213","title":"PDX-1: A Promising Therapeutic Target to Reverse Diabetes.","date":"2022","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/36551213","citation_count":44,"is_preprint":false},{"pmid":"22374871","id":"PMC_22374871","title":"miR-199b-5p directly targets PODXL and DDR1 and decreased levels of miR-199b-5p correlate with elevated expressions of PODXL and DDR1 in acute myeloid leukemia.","date":"2012","source":"American journal of hematology","url":"https://pubmed.ncbi.nlm.nih.gov/22374871","citation_count":44,"is_preprint":false},{"pmid":"18508668","id":"PMC_18508668","title":"PDX-1 functions as a master factor in the pancreas.","date":"2008","source":"Frontiers in bioscience : a journal and virtual library","url":"https://pubmed.ncbi.nlm.nih.gov/18508668","citation_count":44,"is_preprint":false},{"pmid":"16938521","id":"PMC_16938521","title":"Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma.","date":"2006","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/16938521","citation_count":42,"is_preprint":false},{"pmid":"27294148","id":"PMC_27294148","title":"Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX.","date":"2016","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/27294148","citation_count":42,"is_preprint":false},{"pmid":"15486225","id":"PMC_15486225","title":"Cell-specific expression of glucose-dependent-insulinotropic polypeptide is regulated by the transcription factor PDX-1.","date":"2004","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/15486225","citation_count":42,"is_preprint":false},{"pmid":"30389682","id":"PMC_30389682","title":"PDX models recapitulate the genetic and epigenetic landscape of pediatric T-cell leukemia.","date":"2018","source":"EMBO molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/30389682","citation_count":40,"is_preprint":false},{"pmid":"19689288","id":"PMC_19689288","title":"Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells.","date":"2009","source":"Current medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19689288","citation_count":39,"is_preprint":false},{"pmid":"16405074","id":"PMC_16405074","title":"PDX-1 protein is internalized by lipid raft-dependent macropinocytosis.","date":"2005","source":"Cell transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/16405074","citation_count":39,"is_preprint":false},{"pmid":"17449132","id":"PMC_17449132","title":"Role of PDX-1 and MafA as a potential therapeutic target for diabetes.","date":"2007","source":"Diabetes research and clinical practice","url":"https://pubmed.ncbi.nlm.nih.gov/17449132","citation_count":38,"is_preprint":false},{"pmid":"20339896","id":"PMC_20339896","title":"CK2 phosphorylation of Pdx-1 regulates its transcription factor activity.","date":"2010","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/20339896","citation_count":38,"is_preprint":false},{"pmid":"32331230","id":"PMC_32331230","title":"Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy.","date":"2020","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/32331230","citation_count":38,"is_preprint":false},{"pmid":"35260570","id":"PMC_35260570","title":"Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.","date":"2022","source":"Signal transduction and targeted therapy","url":"https://pubmed.ncbi.nlm.nih.gov/35260570","citation_count":38,"is_preprint":false},{"pmid":"26892887","id":"PMC_26892887","title":"Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL.","date":"2016","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/26892887","citation_count":35,"is_preprint":false},{"pmid":"28561270","id":"PMC_28561270","title":"Barriers to generating PDX models of HPV-related head and neck cancer.","date":"2017","source":"The Laryngoscope","url":"https://pubmed.ncbi.nlm.nih.gov/28561270","citation_count":35,"is_preprint":false},{"pmid":"33564250","id":"PMC_33564250","title":"Epigenetic Regulation of PDX-1 in Type 2 Diabetes Mellitus.","date":"2021","source":"Diabetes, metabolic syndrome and obesity : targets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33564250","citation_count":34,"is_preprint":false},{"pmid":"36306349","id":"PMC_36306349","title":"Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance.","date":"2022","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/36306349","citation_count":34,"is_preprint":false},{"pmid":"29212548","id":"PMC_29212548","title":"Generation of stable PDX derived cell lines using conditional reprogramming.","date":"2017","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/29212548","citation_count":33,"is_preprint":false},{"pmid":"32764840","id":"PMC_32764840","title":"Patient-derived xenograft (PDX) models: characteristics and points to consider for the process of establishment.","date":"2020","source":"Journal of toxicologic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/32764840","citation_count":33,"is_preprint":false},{"pmid":"38062430","id":"PMC_38062430","title":"Promising preclinical patient-derived organoid (PDO) and xenograft (PDX) models in upper gastrointestinal cancers: progress and challenges.","date":"2023","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38062430","citation_count":32,"is_preprint":false},{"pmid":"39681638","id":"PMC_39681638","title":"PDX models for functional precision oncology and discovery science.","date":"2024","source":"Nature reviews. Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/39681638","citation_count":31,"is_preprint":false},{"pmid":"37703185","id":"PMC_37703185","title":"Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.","date":"2024","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/37703185","citation_count":30,"is_preprint":false},{"pmid":"26864383","id":"PMC_26864383","title":"Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism.","date":"2016","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26864383","citation_count":30,"is_preprint":false},{"pmid":"9862343","id":"PMC_9862343","title":"The gp200-MR6 molecule which is functionally associated with the IL-4 receptor modulates B cell phenotype and is a novel member of the human macrophage mannose receptor family.","date":"1998","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/9862343","citation_count":30,"is_preprint":false},{"pmid":"15300214","id":"PMC_15300214","title":"Hepatic regeneration and enforced PDX-1 expression accelerate transdifferentiation in liver.","date":"2004","source":"Surgery","url":"https://pubmed.ncbi.nlm.nih.gov/15300214","citation_count":30,"is_preprint":false},{"pmid":"35484194","id":"PMC_35484194","title":"DNA-based copy number analysis confirms genomic evolution of PDX models.","date":"2022","source":"NPJ precision oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35484194","citation_count":28,"is_preprint":false},{"pmid":"17583748","id":"PMC_17583748","title":"PDX-1 expression is associated with islet proliferation in vitro and in vivo.","date":"2007","source":"The Journal of surgical research","url":"https://pubmed.ncbi.nlm.nih.gov/17583748","citation_count":28,"is_preprint":false},{"pmid":"21385937","id":"PMC_21385937","title":"Dynamic regulation of PDX-1 and FoxO1 expression by FoxA2 in dexamethasone-induced pancreatic β-cells dysfunction.","date":"2011","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/21385937","citation_count":28,"is_preprint":false},{"pmid":"31887289","id":"PMC_31887289","title":"Andrographolide promotes pancreatic duct cells differentiation into insulin-producing cells by targeting PDX-1.","date":"2019","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/31887289","citation_count":28,"is_preprint":false},{"pmid":"31320385","id":"PMC_31320385","title":"The Altered Transcriptome and DNA Methylation Profiles of Docetaxel Resistance in Breast Cancer PDX Models.","date":"2019","source":"Molecular cancer research : MCR","url":"https://pubmed.ncbi.nlm.nih.gov/31320385","citation_count":27,"is_preprint":false},{"pmid":"20467340","id":"PMC_20467340","title":"Reduced expression of PDX-1 is associated with decreased beta cell function in chronic pancreatitis.","date":"2010","source":"Pancreas","url":"https://pubmed.ncbi.nlm.nih.gov/20467340","citation_count":26,"is_preprint":false},{"pmid":"31391495","id":"PMC_31391495","title":"Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in canine osteosarcoma tumors.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31391495","citation_count":26,"is_preprint":false},{"pmid":"26886504","id":"PMC_26886504","title":"The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells.","date":"2016","source":"Stem cells and development","url":"https://pubmed.ncbi.nlm.nih.gov/26886504","citation_count":25,"is_preprint":false},{"pmid":"24176839","id":"PMC_24176839","title":"Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic β-cells in a pancreatectomy model.","date":"2013","source":"Phytomedicine : international journal of phytotherapy and phytopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/24176839","citation_count":25,"is_preprint":false},{"pmid":"30091943","id":"PMC_30091943","title":"Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer.","date":"2018","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/30091943","citation_count":25,"is_preprint":false},{"pmid":"32735065","id":"PMC_32735065","title":"PDX regulates inflammatory cell infiltration via resident macrophage in LPS-induced lung injury.","date":"2020","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32735065","citation_count":24,"is_preprint":false},{"pmid":"33159291","id":"PMC_33159291","title":"LncRNA BBOX1-AS1 Aggravates the Development of Ovarian Cancer by Sequestering miR-361-3p to Augment PODXL Expression.","date":"2020","source":"Reproductive sciences (Thousand Oaks, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/33159291","citation_count":24,"is_preprint":false},{"pmid":"17682040","id":"PMC_17682040","title":"Ehrlichia canis gp200 contains dominant species-specific antibody epitopes in terminal acidic domains.","date":"2007","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/17682040","citation_count":24,"is_preprint":false},{"pmid":"25845046","id":"PMC_25845046","title":"PDX-1 (pancreatic/duodenal homeobox-1 protein 1).","date":"2014","source":"Pathologica","url":"https://pubmed.ncbi.nlm.nih.gov/25845046","citation_count":23,"is_preprint":false},{"pmid":"32317693","id":"PMC_32317693","title":"Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32317693","citation_count":23,"is_preprint":false},{"pmid":"30368976","id":"PMC_30368976","title":"Generation of PDX-1 mutant porcine blastocysts by introducing CRISPR/Cas9-system into porcine zygotes via electroporation.","date":"2018","source":"Animal science journal = Nihon chikusan Gakkaiho","url":"https://pubmed.ncbi.nlm.nih.gov/30368976","citation_count":23,"is_preprint":false},{"pmid":"14631368","id":"PMC_14631368","title":"Gastric PDX-1 expression in pancreatic metaplasia and endocrine cell hyperplasia in atrophic corpus gastritis.","date":"2004","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/14631368","citation_count":22,"is_preprint":false},{"pmid":"27620967","id":"PMC_27620967","title":"A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.","date":"2016","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/27620967","citation_count":21,"is_preprint":false},{"pmid":"38488813","id":"PMC_38488813","title":"Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series.","date":"2024","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/38488813","citation_count":21,"is_preprint":false},{"pmid":"17690043","id":"PMC_17690043","title":"PDX-1 expression and proliferation of duct epithelial cells after partial pancreatectomy in rats.","date":"2007","source":"Hepatobiliary & pancreatic diseases international : HBPD INT","url":"https://pubmed.ncbi.nlm.nih.gov/17690043","citation_count":21,"is_preprint":false},{"pmid":"32603749","id":"PMC_32603749","title":"Cutaneous T-Cell Lymphoma PDX Drug Screening Platform Identifies Cooperation between Inhibitions of PI3Kα/δ and HDAC.","date":"2020","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/32603749","citation_count":20,"is_preprint":false},{"pmid":"31303270","id":"PMC_31303270","title":"Fidelity of a PDX-CR model for bladder cancer.","date":"2019","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/31303270","citation_count":20,"is_preprint":false},{"pmid":"29713473","id":"PMC_29713473","title":"NKX2.2, PDX-1 and CDX-2 as potential biomarkers to differentiate well-differentiated neuroendocrine tumors.","date":"2018","source":"Biomarker research","url":"https://pubmed.ncbi.nlm.nih.gov/29713473","citation_count":20,"is_preprint":false},{"pmid":"23703573","id":"PMC_23703573","title":"B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic β-cells.","date":"2013","source":"Experimental & molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23703573","citation_count":20,"is_preprint":false},{"pmid":"31759250","id":"PMC_31759250","title":"PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.","date":"2019","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/31759250","citation_count":19,"is_preprint":false},{"pmid":"32984947","id":"PMC_32984947","title":"Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method.","date":"2020","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/32984947","citation_count":19,"is_preprint":false},{"pmid":"37422628","id":"PMC_37422628","title":"Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo.","date":"2023","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/37422628","citation_count":18,"is_preprint":false},{"pmid":"31782983","id":"PMC_31782983","title":"NNT-AS1 enhances bladder cancer cell growth by targeting miR-1301-3p/PODXL axis and activating Wnt pathway.","date":"2019","source":"Neurourology and urodynamics","url":"https://pubmed.ncbi.nlm.nih.gov/31782983","citation_count":18,"is_preprint":false},{"pmid":"34422820","id":"PMC_34422820","title":"TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL.","date":"2021","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/34422820","citation_count":18,"is_preprint":false},{"pmid":"38062117","id":"PMC_38062117","title":"Endometrial cancer PDX-derived organoids (PDXOs) and PDXs with FGFR2c isoform expression are sensitive to FGFR inhibition.","date":"2023","source":"NPJ precision oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38062117","citation_count":18,"is_preprint":false},{"pmid":"18708173","id":"PMC_18708173","title":"PDX-1 interaction and regulation of the Pancreatic Derived Factor (PANDER, FAM3B) promoter.","date":"2008","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/18708173","citation_count":18,"is_preprint":false},{"pmid":"25839229","id":"PMC_25839229","title":"Interferon-γ Decreases Nuclear Localization of Pdx-1 and Triggers β-Cell Dysfunction in Chronic Pancreatitis.","date":"2015","source":"Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research","url":"https://pubmed.ncbi.nlm.nih.gov/25839229","citation_count":18,"is_preprint":false},{"pmid":"28036027","id":"PMC_28036027","title":"The Phosphorylation of PDX-1 by Protein Kinase CK2 Is Crucial for Its Stability.","date":"2016","source":"Pharmaceuticals (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/28036027","citation_count":17,"is_preprint":false},{"pmid":"2963236","id":"PMC_2963236","title":"Human neoplastic cell line distribution, immunoprecipitation and immunohistopathological study of a gp200 cell surface glycoprotein (LCA) detected by a monoclonal antibody elicited with an ALL cell line.","date":"1987","source":"Neoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/2963236","citation_count":17,"is_preprint":false},{"pmid":"18338074","id":"PMC_18338074","title":"Pleiotropic Roles of PDX-1 in the Pancreas.","date":"2008","source":"The review of diabetic studies : RDS","url":"https://pubmed.ncbi.nlm.nih.gov/18338074","citation_count":17,"is_preprint":false},{"pmid":"16023781","id":"PMC_16023781","title":"Cytokines affect PDX-1 expression, insulin and proinsulin secretion from iNOS deficient murine islets.","date":"2005","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/16023781","citation_count":17,"is_preprint":false},{"pmid":"29180680","id":"PMC_29180680","title":"Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29180680","citation_count":17,"is_preprint":false},{"pmid":"8855966","id":"PMC_8855966","title":"Differential expression of gp200-MR6 molecule in benign hyperplasia and down-regulation in invasive carcinoma of the breast.","date":"1996","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/8855966","citation_count":16,"is_preprint":false},{"pmid":"12503852","id":"PMC_12503852","title":"Pancreatic Duodenal Homeobox (PDX-1) in health and disease.","date":"2002","source":"Journal of pediatric endocrinology & metabolism : JPEM","url":"https://pubmed.ncbi.nlm.nih.gov/12503852","citation_count":16,"is_preprint":false},{"pmid":"21821004","id":"PMC_21821004","title":"ATF3 represses PDX-1 expression in pancreatic β-cells.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21821004","citation_count":16,"is_preprint":false},{"pmid":"32762722","id":"PMC_32762722","title":"PDX models of human lung squamous cell carcinoma: consideration of factors in preclinical and co-clinical applications.","date":"2020","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32762722","citation_count":15,"is_preprint":false},{"pmid":"36096977","id":"PMC_36096977","title":"Platelet-derived extracellular vesicles encapsulate microRNA-34c-5p to ameliorate inflammatory response of coronary artery endothelial cells via PODXL-mediated P38 MAPK signaling pathway.","date":"2022","source":"Nutrition, metabolism, and cardiovascular diseases : NMCD","url":"https://pubmed.ncbi.nlm.nih.gov/36096977","citation_count":14,"is_preprint":false},{"pmid":"32546156","id":"PMC_32546156","title":"Mutation of amphioxus Pdx and Cdx demonstrates conserved roles for ParaHox genes in gut, anus and tail patterning.","date":"2020","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/32546156","citation_count":14,"is_preprint":false},{"pmid":"33669730","id":"PMC_33669730","title":"PDX-Derived Ewing's Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures.","date":"2021","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/33669730","citation_count":14,"is_preprint":false},{"pmid":"33326106","id":"PMC_33326106","title":"Ewing Sarcoma PDX Models.","date":"2021","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/33326106","citation_count":13,"is_preprint":false},{"pmid":"37696750","id":"PMC_37696750","title":"PNA-Pdx: Versatile Peptide Nucleic Acid-Based Detection of Nucleic Acids and SNPs.","date":"2023","source":"Analytical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37696750","citation_count":13,"is_preprint":false},{"pmid":"28179377","id":"PMC_28179377","title":"Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction by inhibiting Pdx-1 expression.","date":"2017","source":"Endocrine connections","url":"https://pubmed.ncbi.nlm.nih.gov/28179377","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49367,"output_tokens":3045,"usd":0.096888,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9560,"output_tokens":3009,"usd":0.061512,"stage2_stop_reason":"end_turn"},"total_usd":0.1584,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the corpus, I need to identify papers about PODXL (podocalyxin-like protein, also known as PCLP, Gp200, PODXL1, PDX). \n\nMost papers in this corpus are about PDX-1 (pancreatic duodenal homeobox 1), PDX models (patient-derived xenografts), or other unrelated topics. I need to filter carefully for papers about the PODXL protein specifically.\n\nRelevant PODXL papers:\n- [15] PMID:12504081 - gp200/GCTM-2 is podocalyxin (identity)\n- [8] PMID:18818395 - PODXL in MSC progenitors\n- [30] PMID:22374871 - miR-199b-5p targets PODXL in AML\n- [42] PMID:26892887 - miR-5100 targets PODXL in pancreatic cancer\n- [51] PMID:26864383 - PODXL frameshift mutation causes juvenile Parkinsonism\n- [61] PMID:26886504 - PODXL in pluripotent stem cells\n- [65] PMID:33159291 - lncRNA/miR-361-3p/PODXL axis in ovarian cancer\n- [78] PMID:31759250 - PODXL1 interacts with C5aR in PDAC metastasis\n- [81] PMID:31782983 - NNT-AS1/miR-1301-3p/PODXL axis in bladder cancer\n- [82] PMID:34422820 - TCF3 targets PODXL in spermatogonial stem cells\n- [95] PMID:36096977 - miR-34c-5p targets PODXL via P38 MAPK\n- [52] PMID:9862343 - gp200-MR6 is mannose receptor family (NOT PODXL - this is a different protein)\n- [87] PMID:2963236 - gp200 as LCA - this appears to be leukocyte common antigen, NOT PODXL\n- [91] PMID:8855966 - gp200-MR6 in breast cancer - same mannose receptor, NOT PODXL\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"The embryonal carcinoma tumor antigen gp200 (also known as GCTM-2) was identified as podocalyxin (PODXL) by protein sequencing of gp200 peptides and reactivity with two distinct anti-podocalyxin monoclonal antibodies, establishing PODXL as the first reported podocalyxin expressed on malignant cells.\",\n      \"method\": \"Protein peptide sequencing and monoclonal antibody reactivity assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — peptide sequencing plus two orthogonal antibody validations in a single study confirm molecular identity\",\n      \"pmids\": [\"12504081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PODXL (podocalyxin-like protein) is selectively expressed on early progenitor mesenchymal stem cells (MSCs); RNA interference knockdown of PODXL caused cell aggregation, demonstrating PODXL is required to prevent aggregation in these progenitor cells. PODXL(hi) MSCs showed greater clonogenicity, more efficient differentiation, and enhanced migration to infarcted heart after intravenous infusion compared to PODXL(lo) cells.\",\n      \"method\": \"FACS sorting, RNAi knockdown with phenotypic readout (aggregation), in vivo intravenous infusion with tissue recovery\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi loss-of-function with defined cellular phenotype (aggregation), complemented by in vivo trafficking assay, single lab\",\n      \"pmids\": [\"18818395\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"miR-199b-5p directly targets PODXL in acute myeloid leukemia (AML); 3'UTR-luciferase assays and mimic transfections established PODXL as a direct post-transcriptional target. Overexpression of miR-199b-5p in K562 cells caused significant decrease in collagen IV-induced migration, linking PODXL expression to cell migration.\",\n      \"method\": \"3'UTR-luciferase reporter assay, miRNA mimic transfection, cell migration assay\",\n      \"journal\": \"American journal of hematology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — 3'UTR luciferase plus functional migration assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"22374871\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"miR-5100 directly binds to the 3'UTR of PODXL and post-transcriptionally represses its expression in pancreatic cancer cells; PODXL silencing diminished cell migration and invasion, demonstrating PODXL promotes metastatic properties in pancreatic cancer.\",\n      \"method\": \"3'UTR reporter assay, miRNA overexpression, siRNA knockdown with migration and invasion assays\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — 3'UTR reporter plus loss-of-function phenotypic assays (migration, invasion), single lab, multiple orthogonal methods\",\n      \"pmids\": [\"26892887\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PODXL is a carrier protein for pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81, GCTM2, GP200, mAb84) in human pluripotent stem cells. PODXL is activated by KLF4 during reprogramming. An antibody to the universal PODXL epitope 3D3 causes massive necrosis and apoptosis of human pluripotent stem cells (hPSCs), demonstrating PODXL surface expression mediates cytotoxic antibody sensitivity.\",\n      \"method\": \"Flow cytometry, antibody-mediated cytotoxicity assay, reprogramming with KLF4 overexpression\",\n      \"journal\": \"Stem cells and development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional antibody cytotoxicity assay plus reprogramming experiments, single lab, multiple methods\",\n      \"pmids\": [\"26886504\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"A homozygous frameshift mutation (c.89_90insGTCGCCCC) in exon 1 of PODXL, resulting in loss of protein, segregated with autosomal-recessive juvenile Parkinsonism in a family. Functional validation in differentiated PC12 cells showed significant differences in neurite branching and length between wild-type and mutant PODXL constructs, establishing a role for PODXL in neuronal morphology.\",\n      \"method\": \"Whole-exome sequencing, Sanger sequencing for segregation, functional assay in PC12 cells (neurite branching/length measurement)\",\n      \"journal\": \"Journal of medical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function genetic variant with functional PC12 cell validation, single lab, two orthogonal approaches\",\n      \"pmids\": [\"26864383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PODXL1 binds directly to C5aR (complement component 5a receptor), stabilizing C5aR protein and recruiting it to the cancer cell plasma membrane to receive C5a; PODXL1 knockout in pancreatic ductal adenocarcinoma (PDAC) cells abolished their metastatic property in a liver metastatic mouse model. C5a stimulation of PODXL1-expressing cells triggered epithelial-mesenchymal transition (EMT), demonstrating PODXL1 promotes PDAC metastasis via the C5aR/C5a axis.\",\n      \"method\": \"Co-immunoprecipitation/direct binding assay, PODXL1 knockout (in vitro and in vivo), liver metastasis mouse model, EMT assay, anti-C5a neutralizing antibody treatment\",\n      \"journal\": \"Neoplasia (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal binding assay, in vitro functional assays, and in vivo knockout metastasis model with antibody validation, multiple orthogonal methods in single study\",\n      \"pmids\": [\"31759250\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TCF3 transcription factor directly regulates PODXL transcription in human spermatogonial stem cells (SSCs), as demonstrated by ChIP assay; PODXL silencing compromised stem cell activity of SSCs, establishing PODXL as a downstream effector of TCF3 in maintaining SSC proliferation and suppressing apoptosis.\",\n      \"method\": \"RNA sequencing, chromatin immunoprecipitation (ChIP), siRNA knockdown with proliferation/apoptosis assays\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP assay confirming direct transcriptional regulation plus loss-of-function phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"34422820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"miR-34c-5p (delivered via platelet-derived extracellular vesicles) targets PODXL by binding to its 3'UTR; depletion of PODXL by miR-34c-5p blocked the P38 MAPK signaling pathway, thereby attenuating ox-LDL-induced inflammation (IL-1β, IL-6, TNF-α) in human coronary artery endothelial cells.\",\n      \"method\": \"3'UTR luciferase assay, gain- and loss-of-function experiments, P38 MAPK pathway analysis, in vitro cell model and ApoE knockout mouse model\",\n      \"journal\": \"Nutrition, metabolism, and cardiovascular diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — 3'UTR reporter plus pathway inhibition assays and in vivo validation, single lab, multiple methods\",\n      \"pmids\": [\"36096977\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PODXL (podocalyxin-like protein) is a sialomucin-family cell surface glycoprotein that carries pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81) in stem cells, prevents cell aggregation in MSC progenitors, promotes cancer cell migration and invasion by physically interacting with C5aR to stabilize it at the plasma membrane and mediate C5a-induced EMT, and contributes to neuronal morphology; its expression is post-transcriptionally regulated by multiple miRNAs (miR-199b-5p, miR-5100, miR-34c-5p, miR-1301-3p, miR-361-3p) and transcriptionally by TCF3, with downstream signaling through the P38 MAPK pathway.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PODXL (podocalyxin-like protein) is a cell-surface sialomucin that controls cell adhesion, migration, and surface receptor presentation across stem cell, cancer, and neuronal contexts [#1, #6]. In pluripotent and progenitor cells it functions as the carrier of pluripotency-associated post-translational epitopes (TRA-1-60, TRA-1-81, GCTM-2/gp200), and its abundance is set during reprogramming by KLF4; antibody engagement of its surface epitope is acutely cytotoxic, marking it as a defining surface determinant of these cells [#0, #4]. On mesenchymal stem cell progenitors PODXL acts as an anti-adhesive that prevents cell aggregation, with high-PODXL cells showing greater clonogenicity and migratory capacity [#1]. In cancer, PODXL drives migration, invasion, and metastasis: it binds directly to the complement receptor C5aR, stabilizing it and recruiting it to the plasma membrane so that C5a stimulation triggers epithelial-mesenchymal transition, and its loss abolishes metastatic capacity in vivo [#6]. PODXL expression is constrained post-transcriptionally by multiple 3'UTR-targeting miRNAs and activated transcriptionally by TCF3, with downstream inflammatory signaling proceeding through the P38 MAPK pathway [#3, #7, #8]. A homozygous loss-of-function frameshift mutation in PODXL segregates with autosomal-recessive juvenile Parkinsonism, and mutant PODXL alters neurite branching and length, linking the protein to neuronal morphology [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established the molecular identity of a malignant-cell tumor antigen, resolving that the embryonal carcinoma antigen gp200/GCTM-2 is podocalyxin and that PODXL is expressed on malignant cells.\",\n      \"evidence\": \"Protein peptide sequencing of gp200 with reactivity against two anti-podocalyxin monoclonal antibodies\",\n      \"pmids\": [\"12504081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define a function for PODXL on malignant cells\", \"No mechanism linking the antigen to a signaling or adhesion role\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined an anti-adhesive cellular function for PODXL in progenitor cells, showing it prevents aggregation and marks cells with superior clonogenic and migratory behavior.\",\n      \"evidence\": \"FACS sorting, RNAi knockdown with aggregation readout, and in vivo intravenous infusion/tissue recovery in MSCs\",\n      \"pmids\": [\"18818395\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of the anti-adhesive effect not resolved\", \"Surface partners mediating aggregation prevention not identified\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Connected PODXL abundance to migratory phenotype and identified the first miRNA control point, establishing PODXL as a direct 3'UTR target of miR-199b-5p in AML.\",\n      \"evidence\": \"3'UTR-luciferase reporter, miRNA mimic transfection, and collagen IV-induced migration assay in K562 cells\",\n      \"pmids\": [\"22374871\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream effectors linking PODXL to migration not defined\", \"Single cell-line context\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Cemented PODXL as the carrier of pluripotency surface epitopes and a reprogramming-regulated, cytotoxicity-defining surface marker of human pluripotent stem cells.\",\n      \"evidence\": \"Flow cytometry, antibody-mediated cytotoxicity assay, and KLF4-driven reprogramming\",\n      \"pmids\": [\"26886504\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which surface PODXL engagement triggers necrosis/apoptosis not defined\", \"Glycosylation enzymes generating the epitopes not identified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extended the miRNA-PODXL regulatory axis to solid tumors, showing miR-5100 represses PODXL and that PODXL is required for migration and invasion in pancreatic cancer.\",\n      \"evidence\": \"3'UTR reporter, miRNA overexpression, and siRNA knockdown with migration/invasion assays in pancreatic cancer cells\",\n      \"pmids\": [\"26892887\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signaling mechanism downstream of PODXL not addressed\", \"In vivo metastasis not tested\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Linked PODXL loss to human disease and a neuronal phenotype, implicating PODXL in neurite morphology through a familial Parkinsonism mutation.\",\n      \"evidence\": \"Whole-exome and Sanger sequencing for segregation plus neurite branching/length assay in PC12 cells\",\n      \"pmids\": [\"26864383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which PODXL shapes neurite morphology unknown\", \"Single family; neuronal signaling partners not identified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Provided the most direct mechanism for PODXL-driven metastasis, showing it binds and stabilizes C5aR at the plasma membrane to enable C5a-induced EMT.\",\n      \"evidence\": \"Co-immunoprecipitation/direct binding, PODXL1 knockout in vitro and in a liver metastasis mouse model, EMT assays, and anti-C5a neutralizing antibody\",\n      \"pmids\": [\"31759250\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the PODXL1-C5aR interaction not resolved\", \"Whether this axis operates in non-PDAC tumors not established\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified upstream transcriptional control of PODXL, establishing it as a direct TCF3 target required for spermatogonial stem cell maintenance.\",\n      \"evidence\": \"RNA-seq, ChIP, and siRNA knockdown with proliferation/apoptosis assays in human SSCs\",\n      \"pmids\": [\"34422820\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which PODXL sustains SSC proliferation not defined\", \"Surface signaling output in SSCs not characterized\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed PODXL within an inflammatory signaling cascade, showing miR-34c-5p repression of PODXL blocks P38 MAPK and attenuates endothelial inflammation.\",\n      \"evidence\": \"3'UTR luciferase, gain/loss-of-function, P38 MAPK pathway analysis, and ApoE-knockout mouse model\",\n      \"pmids\": [\"36096977\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How PODXL couples to P38 MAPK activation not defined\", \"Direct membrane partners in endothelial cells not identified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PODXL's extracellular sialomucin/anti-adhesive properties are mechanistically integrated with its receptor-stabilizing and intracellular signaling functions across these diverse cell types remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of PODXL or its receptor complexes\", \"Cytoplasmic adaptors transducing PODXL signals not defined in the corpus\", \"Glycan-epitope biosynthetic machinery not identified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [6, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [6, 8]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"C5AR1\", \"KLF4\", \"TCF3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}