Affinage

CDX2

Homeobox protein CDX-2 · UniProt Q99626

Length
313 aa
Mass
33.5 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDX2 is a caudal-type homeodomain transcription factor that binds CDX-response elements to enforce intestinal and trophectoderm identity, with context-dependent activating and repressive functions across early development, gut homeostasis, and tumor suppression (PMID:15788452, PMID:12404231, PMID:26489894). In the preimplantation embryo, CDX2 acts cell-autonomously downstream of inside/outside positional cues to repress the pluripotency factors Oct4 and Nanog in outer trophectoderm cells, with which it forms a reciprocal cross-repressive circuit; maternal CDX2 mRNA additionally contributes to cell polarization and compaction (PMID:15788452, PMID:18067887, PMID:20430022, PMID:19564890). In the gut, CDX2 directly transactivates a battery of intestine-specific genes — LI-cadherin/CDH17, lactase, hephaestin, furin, TFF3, villin, and AMACR — and its gastric expression alone is sufficient to drive intestinal metaplasia (PMID:12404231, PMID:10611160, PMID:15825077, PMID:16239403, PMID:17182120, PMID:11875002, PMID:33755595). CDX2 transactivation requires recruitment of the Brm-type SWI/SNF chromatin-remodeling complex through direct protein-protein interaction (PMID:19371634). Beyond differentiation genes, CDX2 controls enterocyte apical-basolateral polarity via the direct targets Rab11a and Kif3b, sustains Lgr5+ stem cell proliferation through largely anticipatory chromatin binding, and tunes Wnt/β-catenin output by activating APC and AXIN2 (PMID:20551175, PMID:23393221, PMID:26489894). CDX2 functions as a tumor suppressor in the gut: it restrains NF-κB-driven inflammation by binding p65 and suppressing COX-2, dampens NLRP3 inflammasome activity through transcriptional activation of TRIM31, and antagonizes migration and metastasis, while its loss cooperates with BRAFV600E to drive serrated tumorigenesis (PMID:15013430, PMID:17599044, PMID:35985421, PMID:28072391, PMID:29439001). CDX2 is itself a tightly regulated node: it is induced by BMP/SMAD, bile-acid/FXR, AMPK, KAT8-mediated H4K16ac, and β-catenin signaling, and repressed by miR-9, MEX3A, Ascl2, and the H3K4me3 demethylase JARID1B (PMID:28234358, PMID:21225631, PMID:22791809, PMID:24284205, PMID:20104269, PMID:38961108, PMID:26307678, PMID:33109187, PMID:23408853).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Establishing that CDX2 is not merely a marker but a master driver of intestinal identity required showing it could impose that program on a foreign tissue.

    Evidence Foxa3-driven Cdx2 transgenic mice directing Cdx2 to gastric mucosa, with histology and gene expression

    PMID:11875002

    Open questions at the time
    • Did not resolve which direct targets are necessary for metaplasia
    • Mechanism of cell-of-origin susceptibility not addressed
  2. 2002 High

    Defining how CDX2 executes the intestinal program at the gene level began with identifying direct cis-targets in differentiation genes.

    Evidence ChIP, reporter assays, and rapid ligand-regulated CDX2 induction in HT-29 cells for LI-cadherin/CDH17, lactase, hephaestin and furin promoters

    PMID:10611160 PMID:12404231 PMID:15825077 PMID:16239403

    Open questions at the time
    • Cofactor requirements at individual promoters not initially defined
    • Hierarchy among targets in driving differentiation unresolved
  3. 2003 Medium

    Understanding why CDX2 is silenced in colon cancer addressed whether loss is epigenetic or genetic and whether restoration is functionally protective.

    Evidence Nuclear run-off, 5-aza-dC/TSA treatment, somatic cell hybrids, and CDX2 re-expression with soft-agar assay in HT-29 cells

    PMID:12947088

    Open questions at the time
    • Identity of the dominant trans-acting repressor not determined
    • In vivo relevance of soft-agar suppression not tested
  4. 2005 High

    Determining the molecular basis of trophectoderm/ICM lineage segregation showed CDX2 is essential to repress pluripotency genes in outer cells.

    Evidence Homozygous Cdx2 knockout mouse blastocysts analyzed by immunofluorescence and in situ hybridization

    PMID:15788452

    Open questions at the time
    • Direct vs. indirect repression of Oct4/Nanog not resolved here
    • Upstream positional inputs unaddressed
  5. 2007 High

    Placing CDX2 in the lineage decision hierarchy clarified whether it reads positional information or generates it.

    Evidence Chimeric blastocyst analysis with Cdx2 mutant ES cells and live embryo tracking

    PMID:18067887

    Open questions at the time
    • Molecular nature of the inside/outside signal upstream of CDX2 not defined
  6. 2009 High

    Defining the reciprocity of the pluripotency-vs-trophectoderm switch showed CDX2 and Nanog mutually repress each other's promoters.

    Evidence ChIP, luciferase reporter assays, and conditional TE differentiation ES cell line

    PMID:19564890

    Open questions at the time
    • Cofactors stabilizing the bistable switch not identified
  7. 2009 High

    Mapping how CDX2 acts in axial patterning and chromatin established direct caudalizing targets and the requirement for a remodeling complex.

    Evidence Conditional Cdx2 KO with ChIP for T/Wnt3a/Cyp26a1 and Cdx4; GST pull-down and ChIP showing CDX2-Brm/SWI-SNF recruitment to the villin promoter

    PMID:19371634 PMID:19906845 PMID:20933081

    Open questions at the time
    • Which SWI/SNF subunit mediates the direct contact not pinpointed
    • Generality of SWI/SNF dependence across CDX2 targets untested
  8. 2010 High

    Extending CDX2 function beyond gene activation revealed it organizes enterocyte polarity and that maternal mRNA contributes to early polarization.

    Evidence Intestine-specific conditional Cdx2 KO with Rab11a/Kif3b suppression recapitulation; maternal+zygotic Cdx2 depletion by dsRNAi/siRNA/morpholino with polarity markers

    PMID:20430022 PMID:20551175

    Open questions at the time
    • How a transcription factor coordinates a whole trafficking network mechanistically not fully resolved
  9. 2015 High

    Distinguishing CDX2's stem-cell role from its villus role showed it is required in Lgr5+ ISCs with anticipatory, bifunctional chromatin occupancy.

    Evidence ISC-specific Cdx2 deletion, ChIP-seq, and mRNA profiling of Lgr5+ ISCs vs villus cells

    PMID:26489894

    Open questions at the time
    • Switch determining activation vs repression at bound sites unknown
    • Partner factors specifying ISC vs villus programs unidentified
  10. 2017 Medium

    Establishing CDX2 as a tumor suppressor in vivo showed its loss cooperates with oncogenic BRAF to drive serrated carcinogenesis.

    Evidence CDX2-conditional KO combined with BRAFV600E knock-in in mouse intestine and organoids

    PMID:28072391

    Open questions at the time
    • Direct targets mediating serrated phenotype not defined
    • Whether CDX2 restoration reverses established tumors untested
  11. 2018 Medium

    Refining the tumor-suppressor mechanism revealed a non-cell-autonomous mode in which CDX2-null metaplastic cells modify the microenvironment to promote tumorigenesis in neighbors.

    Evidence Mosaic conditional Cdx2 KO in adult intestine with NF-κB/iNOS pathway analysis and adjacent-cell tumorigenesis assessment

    PMID:29439001

    Open questions at the time
    • Secreted mediators bridging metaplastic and tumor-prone cells not identified
  12. 2022 Medium

    Connecting CDX2 to inflammasome control identified TRIM31 as the target linking CDX2 loss to NLRP3-driven cytokine release.

    Evidence Conditional Cdx KO mouse with TRIM31 target validation, cytokine measurement, and NLRP3 inhibitor rescue

    PMID:35985421

    Open questions at the time
    • Direct CDX2 occupancy of the TRIM31 promoter not shown here
    • Relative contribution of NLRP3-independent NF-κB unresolved
  13. 2024 High

    Defining upstream control of CDX2 in trophoblast stem cells showed KAT8-deposited H4K16ac is required for CDX2 activation, opposed by SIRT1.

    Evidence Trophoblast Kat8 conditional KO, CUT&Tag for H4K16ac, CDX2 rescue, and SIRT1 inhibitor EX527 in trophoblast organoids

    PMID:38961108

    Open questions at the time
    • How KAT8 is recruited to the CDX2 locus not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CDX2's anticipatory, bifunctional chromatin binding is switched between activation and repression at individual loci, and which partner factors dictate this in stem cells versus differentiated cells, remains unresolved.
  • No structural model of CDX2-cofactor complexes on chromatin
  • Determinants of activation vs repression at bound sites unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 3
Partners
NANOGRELASMARCA2

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Cdx2 is required for repression of Oct4 and Nanog in outer trophectoderm cells of the mouse blastocyst; loss of Cdx2 results in failure to downregulate Oct4 and Nanog in outer cells and subsequent death of those cells, demonstrating Cdx2 is essential for ICM/TE lineage segregation. Homozygous Cdx2 knockout mouse embryos analyzed by immunofluorescence and in situ hybridization; loss-of-function with defined molecular phenotype Development (Cambridge, England) High 15788452
2007 Cdx2 acts cell-autonomously downstream of the first lineage allocation decision; Cdx2 mutant cells show cell-autonomous defects in Oct4, Nanog, and Eomesodermin expression but do not preferentially contribute to ICM in chimeric blastocysts, placing Cdx2 downstream of inside/outside positional information. Chimeric blastocyst analysis using Cdx2 mutant ES cells; live embryo tracking and immunofluorescence Developmental biology High 18067887
2010 Maternally provided Cdx2 mRNA contributes to cell polarization (Par3 and aPKC localization) and compaction at the 8- and 16-cell stage; depletion of both maternal and zygotic Cdx2 causes earlier developmental arrest than zygotic depletion alone, with defects in cell polarity and trophectoderm gene expression (Gata3, Eomes). dsRNAi, siRNAi, and morpholino oligonucleotide depletion of maternal + zygotic Cdx2; immunofluorescence for polarity markers Developmental biology High 20430022
2009 Nanog and Cdx2 bind to and repress each other's promoters, establishing reciprocal transcriptional cross-repression between the pluripotency and trophectoderm programs. Chromatin immunoprecipitation (ChIP), reporter luciferase assays, conditional TE differentiation ES cell line with Nanog overexpression/knockdown Cell research High 19564890
2009 Cdx2 directly regulates axial elongation genes T (Brachyury), Wnt3a, and Cyp26a1, acting as an integrator of caudalizing information through both Hox-independent (axial elongation) and Hox-dependent (somite patterning) pathways. Conditional Cdx2 knockout (tamoxifen-inducible Cre on floxed allele); ChIP to demonstrate direct occupancy of T, Wnt3a, Cyp26a1 promoters; gene expression analysis Development (Cambridge, England) High 19906845
2002 CDX2 directly binds to two CDX2-responsive elements in the 5'-flanking region of the liver-intestine cadherin (LI-cadherin/CDH17) gene and activates its transcription; CDX2 binding demonstrated by chromatin immunoprecipitation; LI-cadherin expression is tightly correlated with CDX2 in colorectal cancers and intestinal metaplasias. High-density oligonucleotide arrays in CDX2-engineered HT-29 cells; ligand-regulated CDX2 activation in presence of protein synthesis inhibitor; ChIP; 5'-flanking region reporter assays Gastroenterology High 12404231
2000 Cdx2 protein binds the TTTAC caudal-related protein binding site in the lactase gene promoter (CE-LPH1) and activates transcription; CDX2-binding complex is more abundant in differentiated enterocytes; CDX2 expression construct activates endogenous lactase mRNA. Electrophoretic mobility shift assay (EMSA) with Cdx2 antibody supershift; luciferase reporter assays with wild-type and mutant promoter; Cdx2 expression construct transfection Gastroenterology High 10611160
2005 CDX2 directly regulates transcription of hephaestin (HEPH), an iron transport protein; CDX2 activation rapidly induces HEPH expression (insensitive to protein synthesis inhibitors), and CDX2 occupies HEPH regulatory regions by ChIP; CDX2 induction suppresses intracellular iron levels via HEPH-mediated iron export; elevated intracellular iron increases CDX2 expression, forming a regulatory loop. Microarrays in CDX2-transduced HT-29/WiDr cells; ligand-regulated CDX2; RNA interference; ChIP; intracellular iron assay Gastroenterology High 15825077
2005 CDX2 directly activates the furin P1 promoter by binding to the CBS2 site (nt -1827 to -1821); CDX2-mediated furin induction correlates with intestinal epithelial differentiation, and furin inhibition impairs LPH activity and enterocyte morphological differentiation. Microarray; transient transfection reporter assays; EMSA with supershift and site-specific mutagenesis; ChIP; in situ hybridization; furin inhibitor treatment American journal of physiology. Gastrointestinal and liver physiology High 16239403
2009 Cdx2 directly binds to predicted Cdx response elements in the Cdx4 promoter and activates its transcription; in vivo occupancy of the Cdx4 promoter by Cdx2 confirmed by ChIP from embryos; Cdx2 and canonical Wnt signaling regulate Cdx4 through distinct mechanisms. Transient transfection reporter assays; EMSA with site-specific mutagenesis of Cdx response elements; ChIP from embryos Mechanisms of development High 20933081
2009 Cdx2 recruits the Brm-type SWI/SNF chromatin remodeling complex to the villin promoter via a direct protein-protein interaction with SWI/SNF subunits; both Cdx2 binding and Brm are required for villin expression in gastrointestinal cells. GST pull-down assays showing direct Cdx2–SWI/SNF subunit interaction; ChIP showing co-recruitment of Cdx2 and Brm to the HCR-Cdx region; reporter assays; knockdown in SW480 cells Experimental cell research High 19371634
2010 Cdx2 controls apical-basolateral polarity in mouse enterocytes in vivo by regulating a gene network involved in endo-lysosomal maturation and apical protein transport; conditional Cdx2 ablation causes defective protein trafficking, ectopic lumen formation, and severe microvillus atrophy; Rab11a and Kif3b are direct Cdx2 targets mediating apical transport. Conditional intestine-specific Cdx2 knockout; 3D tissue culture; gene expression profiling; targeted suppression of Rab11a and Kif3b to recapitulate phenotype Genes & development High 20551175
2013 MEX3A RNA-binding protein represses CDX2 expression post-transcriptionally by binding a specific determinant in the CDX2 mRNA 3'UTR; MEX3A impairs intestinal differentiation, affects cell cycle progression, and promotes expression of intestinal stem cell markers (LGR5, BMI1, MSI1). Genome-wide 3D culture screening; cell-based assays with MEX3A overexpression/knockdown; luciferase 3'UTR reporter assay; murine intestine expression studies Nucleic acids research Medium 23408853
2004 CDX2 down-regulates COX-2 promoter activity by physically interacting with the p65 subunit of NF-κB and inhibiting p65-induced NF-κB transcriptional activity; CDX2 co-immunoprecipitates with p65 in colon cancer cells. Co-immunoprecipitation; luciferase reporter assays; ectopic CDX2 expression in colorectal cancer cells; PMA stimulation Biochemical and biophysical research communications Medium 15013430
2006 CDX2 directly activates TFF3 transcription by binding to at least two CDX-binding sites in the human TFF3 promoter, with the proximal site at -63 being most important; CDX2 overexpression induces endogenous TFF3 mRNA in AGS gastric cells. Luciferase reporter assays with deletion constructs; EMSA identifying CDX-binding sites; stable CDX2 transfection in AGS cells Regulatory peptides Medium 17182120
2013 CDX2 activates APC and AXIN2 promoter activities via intestinal cell-specific enhancer elements; suppressed CDX2 expression is associated with downregulation of APC and AXIN2 and elevated nuclear β-catenin in migrating colon cancer cells, linking CDX2 loss to Wnt/β-catenin pathway activation at the invasive front. Transient transfection of promoter/enhancer reporter constructs; CDX2 knockdown with measurement of endogenous APC, AXIN2; immunohistochemistry of invasive front in vivo Carcinogenesis Medium 23393221
2012 CDX2 drives KLF4 repression in AML cells through tissue-specific patterns of promoter binding and epigenetic modifications; CDX2 differentially regulates KLF4 in AML versus colon cancer cells; PPARγ agonists de-repress KLF4 and are preferentially toxic to CDX2+ leukemic cells. ChIP for CDX2 promoter binding; gene expression in CDX2-expressing AML vs. colon cancer cells; PPARγ agonist treatment; functional toxicity assays The Journal of clinical investigation Medium 23202735
2015 CDX2 is required in Lgr5+ intestinal stem cells (ISCs) for proliferation and long-term production of mature lineages; CDX2 occupancy in ISCs is largely anticipatory (bound before gene activation), and CDX2 both activates and represses direct ISC targets—distinct from its predominantly activating role in villus cells. RNA sequencing of Lgr5+ ISCs vs. villus cells; CDX2-specific deletion in Lgr5+ ISCs; ChIP-seq for CDX2 binding in ISCs; mRNA profiling of control vs. Cdx2−/− ISCs Stem cell reports High 26489894
2015 Cdx2 cooperates with Foxa2 and Nkx2-1 to suppress the metastatic program in lung adenocarcinoma; simultaneous knockdown of all three transcription factors is sufficient to promote metastatic potential of non-metastatic cells, including up-regulation of invadopodia component Tks5long, Hmga2, and Snail. ShRNA knockdown of Cdx2/Foxa2/Nkx2-1 alone and in combination; in vivo metastasis assays; gene expression profiling; genetically engineered mouse model Genes & development Medium 26341558
2002 Gastric expression of Cdx2 alone is sufficient to induce intestinal metaplasia (alcian blue-positive goblet cells and intestine-specific gene expression) in transgenic mice, establishing a causal role for Cdx2 in intestinal transdifferentiation of the stomach. Foxa3/Cdx2 transgenic mice directing Cdx2 to gastric mucosa; histological and gene expression analysis Gastroenterology High 11875002
2003 CDX2 silencing in colon cancer operates through a dominant trans-acting repression mechanism rather than DNA methylation or histone deacetylation; somatic cell hybrids between CDX2-expressing and CDX2-negative lines all showed reduced CDX2, indicating a dominant repressor pathway; a ~9.5-kb 5'-flanking region contains key cis-elements for CDX2 transcription; restoration of CDX2 suppresses proliferation and soft agar growth in HT-29 cells. Nuclear run-off assays; 5-aza-dC and TSA treatment; somatic cell hybrid fusions; CDX2 expression restoration in CDX2-negative HT-29; soft agar assay The Journal of biological chemistry Medium 12947088
2007 Cdx2 expression is reduced during wound healing by transcription factors Snail and Slug (epithelial-mesenchymal transition factors), which can repress Cdx2 transcription; forced Cdx2 expression retards wound repair and reduces migration in colon cancer cell lines; Cdx2 RNA interference enhances migration; forced Cdx2 expression opposes tumor cell spreading in vivo (nude mouse xenografts). In vitro wound healing assays; RNA interference; forced expression; in vivo xenograft at three sites Oncogene Medium 17599044
2017 AMPK enhances CDX2 expression via epigenetic mechanisms: AMPK inactivation is associated with PRC2-mediated enrichment of repressive H3K27me3 and LSD1-mediated reduction of permissive H3K4me3 at the Cdx2 promoter; CDX2 deficiency abolishes intestinal differentiation promoted by AMPK; epithelial AMPK knockout in vivo reduces CDX2 expression and impairs barrier function. AMPK activator/dominant-negative mutant transfection in Caco-2; ChIP for H3K27me3 and H3K4me3 at Cdx2 promoter; epithelial AMPK conditional KO mouse; transepithelial resistance/FITC-dextran permeability assays Cell death and differentiation High 28234358
2011 miR-9 directly targets the 3'-UTR of CDX2 mRNA to down-regulate CDX2 protein expression; miR-9 overexpression reduces CDX2 protein and its downstream targets (p21, MUC2, TFF3), while miR-9 knockdown restores CDX2 and inhibits cell growth via G1 arrest in gastric cancer cells. Luciferase reporter with CDX2 3'-UTR; pre-miR-9 transfection; anti-miR-9 knockdown; miR-9 and CDX2 protein correlation in cell lines and primary tissues International journal of cancer Medium 21225631
2012 The BMP/SMAD pathway (activated by H. pylori infection) upregulates CDX2 expression while downregulating SOX2 in gastric cells; SMAD4 knockdown impairs these effects; infected mice show BMP pathway upregulation, focal Cdx2 expression, and decreased Sox2; proximity ligation assay confirms SMAD protein interactions. Co-culture of AGS cells with H. pylori or BMP2; SMAD4 knockdown; proximity ligation assay; qPCR and western blot; immunohistochemistry in H. pylori-infected mice Carcinogenesis Medium 22791809
2022 Cdx2 regulates NLRP3 inflammasome activity through transcriptional activation of TRIM31 (an NLRP3 suppressor); conditional Cdx2 loss reduces TRIM31, leading to elevated NLRP3, increased IL-1β and IL-6; NLRP3 inhibition reduces cytokine levels and extends lifespan of Cdx conditional mutants; TNF-α also activates NF-κB independently of NLRP3 in Cdx mutants. Conditional Cdx knockout mouse; cytokine measurement; NLRP3 inhibitor treatment; TRIM31 target gene validation; in silico analysis of UC patients The Journal of biological chemistry Medium 35985421
2013 β-catenin signaling directly regulates Cdx2 expression in the dorsal posterior neuropore; conditional β-catenin loss represses Cdx2 and Pax3, leading to spina bifida and tail truncation; Pax3 and Cdx2 are identified as novel Wnt/β-catenin downstream targets; both β-catenin and Pax3 are required for Cdx2 expression in the dorsal PNP. Conditional β-catenin knockout in dorsal neural folds; gene expression analysis; Pax3 transgenic rescue experiment showing partial rescue without restoration of Cdx2 Development (Cambridge, England) Medium 24284205
2017 CDX2 loss cooperates with BRAFV600E to drive serrated colorectal tumorigenesis; CDX2Null/BRAFV600E expression in adult mouse intestinal epithelium produces serrated tumors including carcinomas with gastric marker expression; organoids from CDX2Null/BRAFV600E epithelium recapitulate serrated morphology and gene expression. CDX2 conditional knockout combined with BRAFV600E knock-in in mouse intestinal epithelium; organoid culture; gene expression profiling eLife Medium 28072391
2018 Mosaic intestinal Cdx2 knockout causes metaplastic cells that, without themselves becoming tumorigenic, modify the microenvironment to facilitate tumorigenesis in adjacent Cdx2-intact tumor-prone cells via NF-κB activation, induction of inducible nitric oxide synthase, and stochastic Apc loss of function — a non-cell-autonomous tumor suppressor mechanism. Mosaic conditional Cdx2 knockout in adult intestinal epithelium; NF-κB and iNOS pathway analysis; adjacent cell tumorigenesis assessment The Journal of experimental medicine Medium 29439001
2009 Bile acids induce Cdx2 expression in gastric epithelial cells through the farnesoid X receptor (FXR); the FXR agonist GW4064 mimics bile acid-induced Cdx2 and MUC2 upregulation, and the FXR antagonist guggulsterone abolishes both effects. RGM-1 gastric epithelial cells treated with CDCA and FXR agonist/antagonist; qPCR and protein level analysis of Cdx2 and MUC2 Journal of clinical biochemistry and nutrition Medium 20104269
2010 Cdx2 overexpression in the small intestine reduces nuclear β-catenin in Paneth cells (without homeotic posteriorization) and alters crypt base organization, suggesting Cdx2 regulates Wnt/β-catenin transcriptional activity in a cell-type-specific manner in the intestinal epithelium. Villin-Cdx2 transgenic mice; immunohistochemistry for β-catenin, lineage markers; gene expression analysis Gastroenterology Medium 21081128
2024 KAT8-mediated H4K16 acetylation is required for transcriptional activation of CDX2 in trophoblast stem cells; KAT8 knockout reduces H4K16ac at the CDX2 locus, decreasing CDX2 expression and causing TSC self-renewal defects; CDX2 overexpression partially rescues Kat8 KO phenotype; SIRT1 inhibition (EX527) restores H4K16ac and CDX2 levels. Trophoblast-specific Kat8 conditional KO; RNA-seq; CUT&Tag for H4K16ac; CDX2 rescue overexpression; SIRT1 inhibitor EX527 treatment; trophoblast organoids Nature communications High 38961108
2016 Distinct cis-regulatory elements control Cdx2 expression at different developmental stages: one enhancer regulated by Hippo and Notch signaling is active in blastocyst trophectoderm but inactive in post-implantation extraembryonic structures; additional regulatory elements include a stem-cell-specific sequence active in trophoblast stem cells and a separate element active in post-implantation TE. Comparative analysis of Cdx2 enhancer constructs by reporter transgenic assays in blastocyst, trophoblast stem cells, and post-implantation embryo; CRISPR interference Scientific reports Medium 27256674
2015 Achaete-scute-like 2 (Ascl2) represses CDX2 transcription by directly binding to the proximal E-box of the CDX2 promoter; Ascl2 knockdown activates CDX2 expression and promotes goblet cell differentiation; Ascl2 overexpression inhibits CDX2 and MUC2 expression. Luciferase reporter assays with CDX2 promoter constructs; ChIP demonstrating Ascl2 binding to CDX2 proximal E-box; siRNA knockdown and overexpression Oncotarget Medium 26307678
2020 JARID1B, an H3K4me3 demethylase, represses CDX2 expression by demethylation of H3K4me3 at the CDX2 locus; CDX2 is a downstream target mediating JARID1B-driven Wnt/β-catenin signaling and colorectal cancer cell proliferation. ChIP for H3K4me3 at CDX2 locus; JARID1B knockdown/overexpression; transcriptome analysis; CDX2 rescue experiments Cell communication and signaling : CCS Medium 33109187
2021 LIN28B directly binds CDX2 mRNA (demonstrated by RNA-binding protein immunoprecipitation, RIP assay) and enhances CDX2 expression post-transcriptionally, promoting CRC differentiation; CDX2 in turn activates AMACR transcription, which enhances intestinal alkaline phosphatase activity via butyric acid upregulation. RNA-binding protein IP (RIP) assay; CDX2 ChIP-seq identifying AMACR as direct target; subcutaneous xenograft and liver metastasis mouse models JCI insight Medium 33755595
2014 CDX2 enhances trophoblast cell invasiveness by increasing MMP-9 expression and suppressing TIMP-1; PI3K/Akt signaling regulates CDX2 expression in trophoblast cells, as PI3K/Akt inhibition decreases CDX2 levels. CDX2 overexpression in HTR-8/SVneo trophoblast cells; Transwell invasion assays; western blot and qRT-PCR for MMP-9/TIMP-1; PI3K inhibitor treatment Cellular physiology and biochemistry Low 25171776
2019 CDX2 binds the miR-145-5p promoter region and inhibits its transcription, as demonstrated by ChIP; miR-145-5p in turn targets SENP1 3'-UTR to inhibit its translation, establishing a CDX2/miR-145-5p/SENP1 regulatory axis affecting prostate cancer cell invasion and migration. ChIP demonstrating CDX2 binding to miR-145-5p promoter; dual-luciferase reporter for SENP1 3'-UTR; lentiviral miR-145-5p overexpression; invasion/migration Transwell assay Frontiers in oncology Medium 31249806

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst. Development (Cambridge, England) 916 15788452
1997 Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 545 9052785
2000 Cdx1 and cdx2 expression during intestinal development. Gastroenterology 506 11040183
2002 Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology 387 11875002
2007 Cdx2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo. Developmental biology 274 18067887
2003 Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. The Journal of pathology 238 12474224
2002 Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation. Development (Cambridge, England) 238 11959827
2017 AMPK improves gut epithelial differentiation and barrier function via regulating Cdx2 expression. Cell death and differentiation 190 28234358
1997 Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis. International journal of cancer 189 9036867
2002 CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology 183 12404231
2002 Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach. Cancer letters 178 11790453
2003 Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa. Journal of gastroenterology 166 12560917
2002 Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia. Journal of gastroenterology 139 11871772
2011 MiR-9 downregulates CDX2 expression in gastric cancer cells. International journal of cancer 109 21225631
2009 Cross-regulation of the Nanog and Cdx2 promoters. Cell research 95 19564890
2003 Silencing of CDX2 expression in colon cancer via a dominant repression pathway. The Journal of biological chemistry 89 12947088
2007 The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells. Oncogene 86 17599044
2007 CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 86 17906616
2015 Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis. Genes & development 85 26341558
2009 Cdx2 regulation of posterior development through non-Hox targets. Development (Cambridge, England) 83 19906845
2017 BRAFV600E cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. eLife 81 28072391
2010 The role of CDX2 in intestinal homeostasis and inflammation. Biochimica et biophysica acta 81 21126581
1997 Cloning and chromosome assignment of the human CDX2 gene. Annals of human genetics 81 9459001
2000 The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation. Gastroenterology 80 10611160
2013 CDX2 regulation by the RNA-binding protein MEX3A: impact on intestinal differentiation and stemness. Nucleic acids research 79 23408853
2010 Cdx2 regulates endo-lysosomal function and epithelial cell polarity. Genes & development 76 20551175
2019 MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia. Gut 75 30635407
2012 Gastric intestinal metaplasia revisited: function and regulation of CDX2. Trends in molecular medicine 72 22871898
2010 Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo. Developmental biology 69 20430022
2014 Functional characterization of CDX2 during bovine preimplantation development in vitro. Molecular reproduction and development 68 25251051
2009 CDX2 expression in the intestinal-type gastric epithelial neoplasia: frequency and significance. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 68 19820687
2013 β-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation. Development (Cambridge, England) 65 24284205
2004 Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients. Carcinogenesis 65 15498792
2012 Helicobacter pylori and the BMP pathway regulate CDX2 and SOX2 expression in gastric cells. Carcinogenesis 55 22791809
2017 CDX2 is essential for cell proliferation and polarity in porcine blastocysts. Development (Cambridge, England) 53 28219949
2011 CDX1 and CDX2 expression in intestinal metaplasia, dysplasia and gastric cancer. Journal of Korean medical science 50 21532856
2014 The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. Surgical oncology 49 25126956
2012 Notch signaling pathway and Cdx2 expression in the development of Barrett's esophagus. Laboratory investigation; a journal of technical methods and pathology 49 22449796
2010 Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development. Gastroenterology 47 21081128
2012 CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling. The Journal of clinical investigation 46 23202735
2005 CDX2-regulated expression of iron transport protein hephaestin in intestinal and colonic epithelium. Gastroenterology 46 15825077
2008 Aberrant Cdx2 expression in endometrial lesions with squamous differentiation: important role of Cdx2 in squamous morula formation. Human pathology 44 18495206
2013 Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis 43 23393221
2012 CDX2 expression in columnar cell variant of papillary thyroid carcinoma. American journal of clinical pathology 42 22523209
2009 Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells. Journal of clinical biochemistry and nutrition 42 20104269
2018 The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non-cell-autonomous mechanisms. The Journal of experimental medicine 38 29439001
2008 Expression of homeodomain protein CDX2 in colorectal adenoma and adenocarcinoma. Histology and histopathology 37 18581275
2015 Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells. Stem cell reports 36 26489894
2001 The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis. British journal of cancer 36 11161380
2008 Expression of Cdx2 and claudin-2 in the multistage tissue of gastric carcinogenesis. Oncology 35 18500171
2019 Nuclear β-catenin and CDX2 expression in ovarian endometrioid carcinoma identify patients with favourable outcome. Histopathology 34 30326146
2005 The CDX2 transcription factor regulates furin expression during intestinal epithelial cell differentiation. American journal of physiology. Gastrointestinal and liver physiology 34 16239403
2009 Cdx2 and the Brm-type SWI/SNF complex cooperatively regulate villin expression in gastrointestinal cells. Experimental cell research 33 19371634
2017 Association between Vitamin D receptor (Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and Poly (A)) gene polymorphism and breast cancer: A systematic review and meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 29072133
2014 CDX2 enhances HTR-8/SVneo trophoblast cell invasion by altering the expression of matrix metalloproteinases. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 31 25171776
2016 Expression Pattern of CDX2, Estrogen and Progesterone Receptors in Primary Gastroenteropancreatic Neuroendocrine Tumors and Metastases. Anticancer research 29 26976979
2005 Expression of CDX2 and MUC2 in Barrett's mucosa. Pathology, research and practice 29 16259110
2009 Aberrant expression of the homeobox gene CDX2 in pediatric acute lymphoblastic leukemia. Blood 28 19218548
2005 CDX2 polymorphisms, RNA expression, and risk of colorectal cancer. Cancer research 28 15994917
2022 Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL. Blood 27 35316324
2012 Expression and significance of homeodomain protein Cdx2 in gastric carcinoma and precancerous lesions. World journal of gastroenterology 27 22783055
2009 Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas. Human pathology 27 19800103
2004 Homeodomain protein CDX2 regulates COX-2 expression in colorectal cancer. Biochemical and biophysical research communications 26 15013430
2023 Functional role of GATA3 and CDX2 in lineage specification during bovine early embryonic development. Reproduction (Cambridge, England) 25 36630554
2018 CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the diagnosis of pilomatrical carcinoma. Journal of cutaneous pathology 25 29369390
2014 The role of CDX2 in inflammatory bowel disease. Danish medical journal 25 24814920
2020 JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level. Cell communication and signaling : CCS 24 33109187
2005 Expression of homeodomain protein CDX2 in gallbladder carcinomas. Journal of cancer research and clinical oncology 24 15645288
2019 Wnt3a Activates the WNT-YAP/TAZ Pathway to Sustain CDX2 Expression in Bovine Trophoblast Stem Cells. DNA and cell biology 23 30896984
2019 Multipotent fetal-derived Cdx2 cells from placenta regenerate the heart. Proceedings of the National Academy of Sciences of the United States of America 22 31109997
2006 Regulation of TFF3 expression by homeodomain protein CDX2. Regulatory peptides 22 17182120
2024 KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2. Nature communications 21 38961108
2022 The transcription factor Cdx2 regulates inflammasome activity through expression of the NLRP3 suppressor TRIM31 to maintain intestinal homeostasis. The Journal of biological chemistry 20 35985421
2012 Expression of CDX2 and villin in gastric cardiac intestinal metaplasia and the relation with gastric cardiac carcinogenesis. Asian Pacific journal of cancer prevention : APJCP 20 22502678
2020 Hematopoietic stem and progenitor cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia. Nature communications 19 32541670
2016 Distinct mechanisms regulate Cdx2 expression in the blastocyst and in trophoblast stem cells. Scientific reports 19 27256674
2018 The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas. Annals of diagnostic pathology 18 30236546
2019 Cdx2 Animal Models Reveal Developmental Origins of Cancers. Genes 17 31739541
2015 Achaete scute-like 2 suppresses CDX2 expression and inhibits intestinal neoplastic epithelial cell differentiation. Oncotarget 17 26307678
2013 Association between vitamin D receptor gene Cdx2 polymorphism and breast cancer susceptibility. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 23821301
2010 The role of Cdx2 in Barrett's metaplasia. Biochemical Society transactions 17 20298184
2008 Sonic hedgehog and CDX2 expression in the stomach. Journal of gastroenterology and hepatology 17 19120891
2010 Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 16 20619754
2006 Expression of phosphorylated ERK1/2 and homeodomain protein CDX2 in cholangiocarcinoma. Journal of cancer research and clinical oncology 16 16794828
2010 Cdx4 is a Cdx2 target gene. Mechanisms of development 15 20933081
2021 LIN28B induces a differentiation program through CDX2 in colon cancer. JCI insight 14 33755595
2019 Regulation of REG4 Expression and Prediction of 5-Fluorouracil Sensitivity by CDX2 in Ovarian Mucinous Carcinoma. Cancer genomics & proteomics 14 31659102
2021 Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study. Histopathology 13 34036629
2019 CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration. Frontiers in oncology 13 31249806
2016 Dynamics of SOX2 and CDX2 Expression in Barrett's Mucosa. Disease markers 13 27766003
2009 CDX2 expression in cutaneous metastatic carcinomas and extramammary Paget's Disease. Anticancer research 13 20044613
2022 Immunohistochemical expression of CK20, CK7, and CDX2 in colorectal carcinoma in correlation with pathomorphological characteristics. Folia medica 12 35851772
2013 Disturbed balance between SOX2 and CDX2 in human vitelline duct anomalies and intestinal duplications. Virchows Archiv : an international journal of pathology 12 23568430
2021 The role of CDX2 in renal tubular lesions during diabetic kidney disease. Aging 11 33621200
2021 CDX2 and Reg IV expression and correlation in gastric cancer. BMC gastroenterology 11 33639844
2020 CDX2, SATB2, GATA3, TTF1, and PAX8 Immunohistochemistry in Krukenberg Tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 11 32045390
2014 New insights into the functions and localization of the homeotic gene CDX2 in gastric cancer. World journal of gastroenterology 11 24744585
2013 Expression and functional role of Cdx2 in intestinal metaplasia of cystitis glandularis. The Journal of urology 11 23545100
2013 Expression patterns of Oct4, Cdx2, Tead4, and Yap1 proteins during blastocyst formation in embryos of the marsupial, Monodelphis domestica Wagner. Evolution & development 11 23607301
2013 The role of CDX2 in Caco-2 cell differentiation. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 11 23958315

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