Affinage

PRRX1

Paired mesoderm homeobox protein 1 · UniProt P54821

Length
245 aa
Mass
27.3 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRRX1 is a paired-related homeodomain transcription factor that serves as a master regulator of mesenchymal cell identity, controlling epithelial-mesenchymal transition (EMT), fibroblast activation, and mesenchymal stem cell fate across bone, adipose, and dermal lineages. PRRX1 directly binds promoters of diverse target genes—including TGF-β1, Sox9, Osx, FAP, MMP13, IL-6, ABCC1, FKBP5, TNC, COL6A3, OLR1, and ANXA6—to activate or repress transcription, and physically interacts with co-regulators such as SRF, FOXM1, TOP2A, DNMT3A, and SOX2 to shape context-dependent transcriptional outputs (PMID:9343429, PMID:30705403, PMID:34214250, PMID:35589735, PMID:38448751). Through its two isoforms (PRRX1a and PRRX1b), it differentially regulates migration versus invasion, suppresses adipogenesis via sustained TGF-β ligand expression, drives fibroblast-to-myofibroblast conversion through super-enhancer remodeling, and controls cancer-associated fibroblast plasticity that influences chemoresistance (PMID:23201163, PMID:23250756, PMID:23355395, PMID:33007300, PMID:35589735). Loss-of-function mutations in the PRRX1 homeodomain cause familial atrial fibrillation through impaired transactivation of cardiac target genes ISL1 and SHOX2, and homeodomain missense variants cause craniosynostosis through defective nuclear localization (PMID:34845933, PMID:37154149).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 High

    Establishing PRRX1 as a transcription factor that activates SRE-dependent gene expression through physical interaction with SRF resolved how a homeodomain protein could regulate serum-responsive genes without acting through enhanced SRF DNA binding.

    Evidence Systematic homeodomain mutagenesis and in vivo transcription assays identifying SRF-contact residues on helices 1/2; separate competition assays showing PRRX1 does not overcome YY1-mediated CArG repression

    PMID:9174170 PMID:9343429

    Open questions at the time
    • Endogenous genomic targets of PRRX1-SRF complexes not identified
    • Crystal structure of PRRX1-SRF complex unavailable
  2. 1999 Medium

    Identification of the NUP98-PRRX1 fusion in AML established that the PRRX1 homeodomain could be co-opted into an oncogenic transcription factor when fused to the NUP98 transactivation domain.

    Evidence Molecular cloning and breakpoint sequencing of t(1;11)(q23;p15) in AML patient samples

    PMID:10397741

    Open questions at the time
    • No functional reconstitution of transformation at this stage
    • Endogenous target genes of the fusion not identified
  3. 2006 High

    Demonstrating that NUP98-PRRX1 recruits HDAC1 via FG repeats to repress PMX1/SRF-mediated transcription, while also binding CBP, revealed how the fusion functions as a dual activator/repressor—a key mechanistic distinction from wild-type PRRX1.

    Evidence Co-immunoprecipitation of HDAC1 and CBP with NUP98-PRRX1, luciferase reporter assays showing trans-repression of c-FOS SRE

    PMID:16651408

    Open questions at the time
    • Genome-wide targets of dual regulation not mapped
    • Relative contribution of activation vs. repression to leukemogenesis unclear
  4. 2008 High

    Showing that NUP98-PMX1 leukemogenesis requires the GLFG domain and homeodomain DNA binding but is independent of SRF interaction clarified that the fusion transforms through homeodomain-directed target gene dysregulation rather than SRF pathway hijacking.

    Evidence Strategic homeodomain mutations disrupting SRF interaction vs. DNA binding tested in retroviral transduction of murine progenitors and in vivo leukemia models; Meis1 collaboration demonstrated

    PMID:18604245

    Open questions at the time
    • Direct transcriptional targets driving transformation not identified
    • Mechanism of Meis1 cooperation unresolved
  5. 2011 High

    Identifying PRRX1 as an obligate mediator of TNF-α-induced suppression of osteoblast differentiation through direct binding to the Osterix promoter placed PRRX1 as a transcriptional repressor in inflammatory bone biology.

    Evidence ChIP confirming PRRX1 binding to Osx promoter, EMSA, siRNA rescue abolishing TNF-mediated Osx suppression in preosteoblasts

    PMID:20683885

    Open questions at the time
    • Whether PRRX1 directly recruits co-repressors to the Osx promoter unknown
    • In vivo bone phenotype of PRRX1 loss in inflammatory setting not tested
  6. 2012 High

    Two landmark studies revealed PRRX1 as both an EMT inducer that uncouples migration/invasion from stemness in cancer and a suppressor of adipogenesis through TGF-β ligand maintenance, establishing its dual role in cell identity and lineage fate decisions.

    Evidence In vivo metastasis assays showing PRRX1 loss enables colonization with MET and stem cell property acquisition; stable knockdown/overexpression with adipogenesis assays and TGF-β inhibitor rescue

    PMID:23201163 PMID:23250756

    Open questions at the time
    • Chromatin-level mechanism of EMT gene regulation by PRRX1 not defined
    • Whether TGF-β2/3 promoters are direct PRRX1 targets not shown by ChIP
  7. 2013 High

    Demonstrating isoform-specific functions—PRRX1b binding the Sox9 promoter to regulate acinar-ductal metaplasia while PRRX1a and PRRX1b differentially control migration vs. invasion—revealed that alternative C-termini direct distinct transcriptional programs.

    Evidence Isoform-specific overexpression, Sox9 promoter binding assays, Prrx1creERT2-IRES-GFP lineage tracing in pancreas

    PMID:23355395

    Open questions at the time
    • Structural basis for isoform-specific DNA target selectivity unknown
    • Genome-wide isoform-specific binding profiles not generated
  8. 2017 High

    Linking PRRX1 to atrial electrophysiology—showing that PRRX1 suppression shortens atrial action potential duration and that a common SNP in a PRRX1 enhancer alters its expression—connected this developmental transcription factor to atrial fibrillation susceptibility.

    Evidence hESC-derived cardiomyocyte and zebrafish knockdown with electrophysiological recordings; enhancer reporter assays validating rs577676 function

    PMID:28974514

    Open questions at the time
    • Direct cardiac transcriptional targets of PRRX1 mediating action potential regulation not identified at this stage
  9. 2019 High

    Identifying FOXM1 as a direct physical partner of PRRX1 (through Co-IP and domain mapping) demonstrated that PRRX1 cooperates with non-homeodomain transcription factors beyond SRF to regulate target gene programs including DNA damage response.

    Evidence Reciprocal Co-IP with domain deletion mapping (PRRX1 aa 200–222 to FOXM1 Forkhead domain), luciferase reporters, loss-of-function rescue in pancreatic cancer cells

    PMID:30705403

    Open questions at the time
    • Genome-wide co-occupancy of PRRX1-FOXM1 not mapped
    • Structural basis of the interaction not resolved
  10. 2020 High

    Revealing that PRRX1 controls cancer-associated fibroblast plasticity—switching between dormant and activated myofibroblastic states—and that Prrx1-deficient CAFs constitutively secrete HGF to drive tumor subtype switching and chemoresistance established PRRX1 as a stromal fate regulator in the tumor microenvironment.

    Evidence Prrx1 genetic depletion in PDAC mouse model, CAF-tumor organoid co-culture, gene expression subtype analysis

    PMID:33007300

    Open questions at the time
    • Direct transcriptional targets mediating CAF state switching not fully catalogued
    • Whether PRRX1 regulates HGF promoter directly not determined
  11. 2021 High

    Multiple studies converged on PRRX1 as a direct promoter-binding activator of TGF-β1 (in glioma), a DNMT3A-recruiting epigenetic silencer of PROM1 (isoform-specific, PRRX1b only), and an upstream controller of MET via the PITX2/miR-200 axis, broadening the repertoire of PRRX1 effector mechanisms beyond simple transcriptional activation.

    Evidence ChIP for TGF-β1 promoter binding with TGF-β1 silencing rescue; Co-IP of PRRX1b-DNMT3A with bisulfite sequencing of PROM1 promoter; epistasis experiments in HCC dissecting PRRX1→PITX2→miR-200→E-cadherin pathway

    PMID:33587761 PMID:34131109 PMID:34214250

    Open questions at the time
    • Whether DNMT3A recruitment is genome-wide or locus-specific unknown
    • PRRX1b structural determinants for DNMT3A selectivity not mapped
  12. 2021 Medium

    Identification of PRRX1 loss-of-function mutations (p.Gln107* and p.Arg146Ile) as causes of familial atrial fibrillation, with diminished transactivation of ISL1 and SHOX2, established PRRX1 haploinsufficiency as a Mendelian arrhythmia mechanism.

    Evidence Whole-exome sequencing in AF families, Sanger confirmation, luciferase reporter assays showing reduced transactivation and promoter binding of mutant PRRX1

    PMID:34845933

    Open questions at the time
    • Independent replication in additional families needed
    • In vivo electrophysiological validation of these specific mutations not performed
    • Whether ISL1/SHOX2 are direct or indirect targets not resolved by ChIP
  13. 2022 High

    Genome-wide super-enhancer profiling established PRRX1 as a master transcription factor that remodels the super-enhancer landscape to convert fibroblasts to myofibroblasts via TGF-β signaling, and fibroblast-specific Prrx1 depletion induced sustained remission of chemotherapy-resistant tumors, demonstrating stromal PRRX1 as a therapeutic vulnerability.

    Evidence ChIP-seq for super-enhancer marks, fibroblast-specific genetic depletion in genetically engineered mouse models of PDAC

    PMID:35589735

    Open questions at the time
    • Which specific super-enhancers are essential for myofibroblast conversion not individually validated
    • Pharmacological targeting strategy not established
  14. 2022 High

    Lineage tracing identified Prrx1-expressing cells as rare adult mesenchymal stem cells for bone, adipose, and dermis, and as a pro-fibrotic fibroblast subpopulation in wound repair, resolving their in vivo identity and tissue-regenerative functions.

    Evidence Knock-in Cre/CreERT2 lineage tracing, cell depletion, transplantation assays, single-cell RNA-seq in dermal wound models and homeostatic tissues

    PMID:33176144 PMID:36456880

    Open questions at the time
    • Transcriptional targets maintaining stemness vs. driving fibrosis in Prrx1+ cells not distinguished
    • Human in vivo equivalence of Prrx1+ stem cell population not demonstrated
  15. 2023 Medium

    Demonstrating that homeodomain missense variants cause aberrant PRRX1 nuclear localization linked homeodomain integrity to nuclear import as a pathogenic mechanism in craniosynostosis.

    Evidence Immunofluorescence of wild-type vs. mutant PRRX1 in patient-derived and transfected cells

    PMID:37154149

    Open questions at the time
    • Nuclear import machinery interacting with PRRX1 homeodomain not identified
    • Rescue experiments restoring nuclear localization not performed
  16. 2024 Medium

    ChIP-validated direct binding of PRRX1 to multiple new promoter targets (TNC, FAP, ANXA6, OLR1) and placement downstream of Twist1 in fibrosis cascades expanded the PRRX1 regulon and solidified its role as a central node in organ fibrosis across kidney, intestine, and heart.

    Evidence ChIP assays for Twist1→Prrx1 promoter and Prrx1→TNC promoter with fibroblast-specific Twist1 KO; ChIP-seq and conditional Prrx1 KO for FAP in intestinal fibrosis; ChIP-PCR for ANXA6 and OLR1 in cancer models

    PMID:39010054 PMID:39181396 PMID:39528080 PMID:41350883

    Open questions at the time
    • Comprehensive genome-wide PRRX1 cistrome across tissue contexts not integrated
    • Co-factor requirements at each target promoter not systematically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The genome-wide binding landscape of endogenous PRRX1 across its major biological contexts (mesenchymal stem cells, fibroblasts, cardiomyocytes, cancer) has not been integrated, and the structural basis for isoform-specific partner selection and target gene discrimination remains unresolved.
  • No crystal or cryo-EM structure of PRRX1 homeodomain with DNA or any partner
  • Integrated multi-tissue PRRX1 ChIP-seq/CUT&RUN atlas absent
  • Isoform-specific regulatory mechanisms at the structural level unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 15 GO:0003677 DNA binding 10 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3
Partners
CBPDNMT3AFOXM1HDAC1SOX2SRFTOP2A

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 PRRX1 is an EMT inducer that confers migratory and invasive properties on carcinoma cells; loss of PRRX1 is required for metastatic colonization in vivo, with reversion to epithelial phenotype concomitant with acquisition of stem cell properties, demonstrating that PRRX1 uncouples EMT and stemness. In vivo metastasis assays, loss-of-function (knockdown) and gain-of-function in cancer cell lines, EMT marker analysis Cancer cell High 23201163
1999 In AML with t(1;11)(q23;p15), NUP98 is fused in-frame to PMX1 (PRRX1); the fusion protein retains the PMX1 homeodomain and the N-terminal GLFG-rich NUP98 transcriptional activation domain, suggesting the fusion acts as an oncogenic transcription factor by upregulating PMX1 homeodomain-driven transcription. Molecular cloning, RT-PCR, translocation breakpoint sequencing Blood Medium 10397741
2006 The NUP98-PMX1 fusion protein trans-represses PMX1/SRF-mediated c-FOS activation by recruiting histone deacetylase 1 (HDAC1) via its FG repeat domains; the FG domains also bind CBP (a coactivator), giving the fusion dual trans-activator and trans-repressor activity. Luciferase reporter assays, co-immunoprecipitation, protein biochemical assays, molecular cloning Cancer research High 16651408
1997 Phox1 (PRRX1 human ortholog) activates the c-fos serum response element (SRE) by interacting with serum response factor (SRF); residues on helices 1 and 2 of the homeodomain (not required for DNA binding) mediate contact with an accessory factor, while major-groove DNA contact is also required for SRE activation in vivo. Detailed homeodomain mutagenesis, in vivo transcription assays, domain-swap experiments Molecular and cellular biology High 9343429
1997 Phox1/MHox (PRRX1) overexpression does not diminish YY1-mediated repression of CArG elements, indicating that Phox1 transcriptional activation at the SRE does not operate through enhanced SRF binding; YY1 represses CArG elements by competing with SRF for overlapping binding sites. In vitro binding competition assays, serial point mutagenesis of CArG element, in vivo overexpression reporter assays DNA and cell biology Medium 9174170
2008 Leukemogenic transformation by NUP98-PMX1 requires the NUP98 GLFG domain and the DNA-binding capability of the PMX1 homeodomain, but is independent of PMX1's ability to interact with SRF; NUP98-PMX1 collaborates with Meis1 to accelerate myeloproliferative leukemia. Strategic homeodomain mutations, retroviral transduction of murine myeloid progenitors, myeloid differentiation and proliferation assays, in vivo leukemia model Oncogene High 18604245
2012 PRRX1a and PRRX1b are negative regulators of adipogenesis; they inhibit PPARγ activity and sustain expression of TGFβ2 and TGFβ3, and their knockdown enhances adipogenesis, which is phenocopied by TGFβ signaling inhibition, establishing a PRRX1→TGFβ→adipogenesis suppression axis. Stable knockdown, transient overexpression, adipogenesis assays, PPARγ reporter assays, TGFβ pathway inhibition, in vivo adipose tissue analysis The Journal of biological chemistry High 23250756
2011 TNF-α stimulates a 14-fold increase in Prx1 (PRRX1) mRNA in preosteoblasts; Prx1 binds the Osterix (Osx) promoter (confirmed by ChIP), and its expression inhibits Osx and RUNX2 transcription; siRNA silencing of Prx1 abrogates TNF-mediated suppression of Osx, identifying Prx1 as an obligate mediator of TNF inhibition of osteoblast differentiation. Protein pull-down from nuclear extracts + mass spectrometry, ChIP assay, siRNA knockdown, transient expression, EMSA Journal of bone and mineral research High 20683885
2013 The PRRX1b isoform specifically binds the Sox9 promoter and positively regulates Sox9 expression in pancreatic cells, placing PRRX1b upstream of Sox9 in a hierarchical axis that influences acinar-ductal metaplasia; the two isoforms, PRRX1a and PRRX1b, regulate migration and invasion respectively in pancreatic cancer cells. Isoform-specific overexpression, promoter binding assays, sorted Prrx1+ cell functional assays, lineage tracing (Prrx1creERT2-IRES-GFP mice) Genes & development High 23355395
2019 PRRX1 directly physically interacts with FOXM1 via the PRRX1A/B 200–222/217 aa region and the FOXM1 Forkhead domain; this interaction mediates cooperative transcriptional regulation of FOXM1-dependent targets and limits induction of DNA damage in pancreatic cancer cells. Co-immunoprecipitation, domain deletion mapping, luciferase reporter assays, loss-of-function and rescue experiments Oncogene High 30705403
2021 PRRX1 directly binds to the promoter region of the TGF-β1 gene, upregulates TGF-β1 expression, and activates the TGF-β/Smad pathway to promote stemness and angiogenesis in glioma; silencing TGF-β1 reverses PRRX1-induced malignant behaviors. Subcellular proteomics, ChIP assay (promoter binding), TGF-β1 silencing rescue experiments, in vivo knockdown Cell death & disease Medium 34131109
2021 Upon BMP stimulation, the PRRX1b (pmx-1b) isoform interacts with DNA methyltransferase DNMT3A and induces promoter methylation of PROM1 (CD133), reducing the CD133-positive glioma-initiating cell population and inhibiting tumorigenicity in vivo; the PRRX1a isoform does not have this activity. Co-immunoprecipitation of PRRX1b-DNMT3A, bisulfite sequencing of PROM1 promoter, DNMT3A silencing rescue, in vivo tumorigenicity assays Molecular oncology High 34214250
2017 Suppression of PRRX1 in human embryonic stem cell-derived cardiomyocytes and embryonic zebrafish results in shortening of the atrial action potential duration, a hallmark of atrial fibrillation; a functional SNP (rs577676) in a PRRX1 enhancer alters enhancer activity and differentially regulates PRRX1 expression in human left atria. hESC-derived cardiomyocyte loss-of-function, zebrafish embryo knockdown, enhancer reporter assays in mouse atrial cell line, electrophysiological action potential measurement Circulation. Cardiovascular genetics High 28974514
2021 PRRX1 loss-of-function mutations (p.Gln107* and p.Arg146Ile) cause familial atrial fibrillation; both mutants show significantly diminished transactivation of downstream target genes ISL1 and SHOX2 and markedly decreased ability to bind their promoters, despite normal intracellular distribution. Whole-exome sequencing, Sanger sequencing, luciferase reporter gene assays (transactivation), promoter-binding assays in HeLa cells Journal of the American Heart Association Medium 34845933
2022 A variant noncoding region regulates Prrx1 expression and, when altered, predisposes to atrial arrhythmias by changing atrial electrophysiology. Functional validation of noncoding variant, in vivo electrophysiological measurements Circulation research Medium 34092116
2022 PRRX1 is a master transcription factor that remodels super-enhancer landscapes to drive fibroblasts toward a myofibroblastic phenotype via TGF-β signaling; fibroblast-specific Prrx1 depletion induces sustained complete remission of chemotherapy-resistant cancer in genetically engineered mouse models. Super-enhancer profiling (ChIP-seq), fibroblast-specific genetic depletion in GEMM, functional in vitro assays, CAF co-culture experiments Nature communications High 35589735
2022 Prrx1-expressing fibroblasts are a lineage-traced pro-fibrotic subpopulation in mouse ventral dermis responsible for acute and chronic fibroses during wound repair, as demonstrated by lineage tracing and single-cell transcriptomics. Lineage tracing (Prrx1-Cre), single-cell RNA sequencing, fibrosis models Cell reports High 33176144
2022 Rare Prrx1-expressing cells act as stem cells for bone, white adipose tissue, and dermis in adult mice; genetic lineage tracing and cell depletion experiments show they are indispensable for tissue homeostasis and repair, and their activity is regulated by Wnt signaling. Knock-in Cre/CreERT2 lineage tracing, cell depletion, single-cell transcriptomics, transplantation assays Nature genetics High 36456880
2020 Prrx1 in cancer-associated fibroblasts is critical for tuning CAF activation state, allowing dynamic switching between dormant and activated (myofibroblastic) states; Prrx1-deficient CAFs remain constitutively activated and alter tumor differentiation and gemcitabine resistance through CAF-derived hepatocyte growth factor. Genetic depletion of Prrx1 in PDAC mouse model, primary fibroblast functional assays, tumor organoid-CAF co-culture, gene expression analysis Gastroenterology High 33007300
2021 PRRX1 knockdown in HCC promotes mesenchymal-to-epithelial transition (MET) and metastatic colonization; mechanistically, PRRX1 deficiency upregulates PITX2, which increases miR-200a and miR-200b/429, which in turn suppress CTNNB1 and SLUG respectively, enabling E-cadherin re-expression. Knockdown/overexpression in HCC cell lines, microarray, animal metastasis model, pathway epistasis experiments Cancer science Medium 33587761
2021 RBMS3 RNA-binding protein stabilizes PRRX1 mRNA post-transcriptionally (shown by actinomycin D mRNA stability assays and RBMS3-PRRX1 mRNA interaction), and PRRX1 is required for RBMS3-mediated EMT in triple-negative breast cancer. Genome-wide mRNA stability assay (actinomycin D chase), RNA-binding protein interaction, loss-of-function rescue experiments Oncogene Medium 34608266
2020 Prrx1 CAF plasticity promotes PDAC tumor squamous subtype and gemcitabine resistance via CAF-derived hepatocyte growth factor (HGF) signaling to tumor cells. CAF-tumor organoid co-culture, gene expression subtype analysis, Prrx1 fibroblast-specific depletion in vivo Gastroenterology Medium 33007300
2024 Twist1 directly binds to the Prrx1 promoter to drive its expression in kidney fibroblasts; Prrx1 in turn directly binds the TNC (tenascin-C) promoter to promote fibroblast activation and kidney fibrosis, establishing a Twist1→Prrx1→TNC signaling axis. ChIP assay (Twist1 binding to Prrx1 promoter; Prrx1 binding to TNC promoter), fibroblast-specific Twist1 knockout mice, gain- and loss-of-function experiments Kidney international High 39181396
2022 PRRX1 promotes resistance to temozolomide in glioma by directly binding the ABCC1 promoter and initiating its transcription, upregulating ABCC1 drug transporter expression; PRRX1 also facilitates vasculogenic mimicry formation as an extrinsic resistance mechanism. ChIP assay (PRRX1 binding to ABCC1 promoter), siRNA knockdown, in vitro and in vivo drug sensitivity assays American journal of cancer research Medium 36119823
2020 PRRX1 directly transactivates the COL6A3 promoter in adipose cells (shown by reporter assay with endogenous COL6A3 promoter), and PRRX1 knockdown reduces COL6A3 mRNA, identifying PRRX1 as a direct transcriptional regulator of COL6A3. Reporter assay (endogenous COL6A3 promoter), siRNA knockdown, stable overexpression in 3T3-L1 cells Scientific reports Medium 33214660
2022 PRRX1 directly binds the MMP13 promoter (validated by luciferase reporter and ChIP assay) and activates MMP13 transcription, which in turn promotes inflammation and barrier dysfunction in colonic epithelial cells. ChIP assay, luciferase reporter assay, siRNA knockdown, overexpression, ELISA, TEER measurement Bioengineered Medium 34967278
2024 PRRX1 promotes OLR1 expression in cancer-associated fibroblasts by recruiting active histone marks H3K27ac and H3K4me3 to the OLR1 locus, activating CAFs to support lung cancer growth and immune evasion. ChIP-seq (H3K27ac, H3K4me3), ChIP-qPCR, luciferase reporter assay, PRRX1 and OLR1 knockdown in CAFs, co-culture experiments Cancer cell international Medium 39010054
2022 The Twist1-Prrx1-TNC positive feedback loop drives cardiac fibroblast activation to myofibroblasts; Prrx1 overexpression promotes cardiac fibroblast proliferation, migration, and myofibroblast transformation, while Prrx1 silencing attenuates TGF-β1-induced cardiac fibrosis in vitro. Overexpression and knockdown of Prrx1 in cardiac fibroblasts, TGF-β1 stimulation, proliferation and migration assays Cell biology international Medium 36273425
2021 PRRX1 directly transactivates the IL-6 promoter (confirmed by JASPAR prediction and dual-luciferase reporter assay), and IL-6 activates JAK2/STAT3 signaling to promote colorectal cancer stemness and chemoresistance. Dual-luciferase reporter assay, GSEA, Western blot, in vivo xenograft, ELISA Journal of gastrointestinal oncology Medium 36636075
2024 PRRX1 co-immunoprecipitates with TOP2A in malignant peripheral nerve sheath tumour (MPNST) cells; overexpressed PRRX1 directly interacts with TOP2A to cooperatively promote EMT and expression of tumour malignancy-related gene sets including mTORC1, KRAS, and SRC signaling pathways. Co-immunoprecipitation, mass spectrometry, RNA-seq, structural prediction, PRRX1 knockdown/overexpression British journal of cancer Medium 38448751
2025 PRRX1 transcriptionally activates FKBP5 (directly promoting FKBP5 expression) and thereby activates p38 MAPK signaling to drive excessive mitophagy and cardiomyocyte ferroptosis during myocardial ischemia/reperfusion injury; PRRX1 silencing is cardioprotective. siRNA knockdown, FKBP5 overexpression rescue, p38 MAPK inhibitor, in vitro OGD/R model, in vivo rat I/R model Biochimica et biophysica acta. Molecular basis of disease Medium 40044064
2024 PRRX1 directly transactivates the FAP (fibroblast activation protein) promoter (confirmed by ChIP-seq and reporter assays), establishing a PRRX1-FAP regulatory axis that drives fibroblast activation and intestinal fibrosis; fibroblast-specific Prrx1 deletion (Col1a2-Cre;Prrx1fl/fl) mitigates DNBS-induced intestinal fibrosis. Single-cell RNA-seq, ChIP-seq, dual-luciferase reporter assays, conditional knockout mouse model, colon proteomics Journal of nanobiotechnology Medium 41350883
2022 Mechanical stimulation enhances release of active TGF-β1, which promotes migration of Prrx1+ cells via ciliary TGF-β signaling; inhibition of TGF-β signaling, knockdown of Pallidin (blocking TGFβR2 translocation to primary cilia), or deletion of Ift88 in Prrx1+ cells all abolish mechanics-induced Prrx1+ cell migration. Single-cell RNA sequencing, in vivo mechanical stimulation models, TGFβ inhibition, Pallidin knockdown, Ift88 conditional deletion in Prrx1+ cells, migration assays eLife Medium 35475783
2021 PRRX1A isoform transcriptionally activates TGF-β expression (shown by correlation with TGF-β and TGF-β/TGFβR signaling), and PRRX1A directly binds and stabilizes SOX2 protein, promoting cancer stem cell sphere formation and self-renewal in non-small cell lung cancer. Isoform-specific overexpression and knockdown, CSC functional assays, co-immunoprecipitation (PRRX1A-SOX2 binding), in vivo mouse models Translational lung cancer research Medium 32676335
2019 Pre-metastatic niche-derived SDF-1 downregulates Prrx1 through STAT3 signaling in hepatocellular carcinoma cells, which in turn increases CXCR4 expression, promoting organ colonization; loss of Prrx1 was negatively correlated with increased CXCR4 in metastatic sites. Prrx1 shRNA knockdown, SDF-1 stimulation, STAT3 pathway inhibition, in vivo xenograft/metastasis assays Journal of experimental & clinical cancer research Medium 31752959
2022 Nicotine inhibits Prrx1 expression in pituitary stem/progenitor cells through epigenetic regulation (first intron hypermethylation of the Prrx1 gene detected by bisulfite sequencing), leading to a delayed supply of GH-producing cells. In vivo nicotine exposure in young rats, bisulfite sequencing, RT-PCR, immunohistochemistry Growth hormone & IGF research Medium 32146343
2023 Heterozygous missense variants within the PRRX1 homeodomain cause abnormal nuclear localization of the PRRX1 protein, establishing that homeodomain missense mutations impair nuclear targeting as a pathogenic mechanism in craniosynostosis. Immunofluorescence analysis of nuclear localization of wild-type vs. mutant PRRX1 proteins in patient-derived and transfected cells Genetics in medicine Medium 37154149
2024 PRRX1 promotes ANXA6 expression transcriptionally (confirmed by ChIP-PCR and dual-luciferase assay), and ANXA6 enhances PKCα/EGFR complex formation, inhibiting EGFR phosphorylation and downstream AKT and ERK1/2, thereby increasing cisplatin sensitivity in bladder cancer. ChIP-PCR, dual-luciferase assay, co-immunoprecipitation (ANXA6-PKCα-EGFR complex), mass spectrometry, immunofluorescence Life sciences Medium 39528080

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer cell 794 23201163
1999 NUP98 is fused to PMX1 homeobox gene in human acute myelogenous leukemia with chromosome translocation t(1;11)(q23;p15). Blood 108 10397741
2014 MiR-124 Radiosensitizes human colorectal cancer cells by targeting PRRX1. PloS one 102 24705396
2013 The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis. Genes & development 97 23355395
2014 The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression. The American journal of pathology 90 24946010
2014 PRRX1 promotes epithelial-mesenchymal transition through the Wnt/β-catenin pathway in gastric cancer. Medical oncology (Northwood, London, England) 84 25428393
2022 PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression. Nature communications 82 35589735
2020 Prrx1 Fibroblasts Represent a Pro-fibrotic Lineage in the Mouse Ventral Dermis. Cell reports 70 33176144
2011 Blastema induction in aneurogenic state and Prrx-1 regulation by MMPs and FGFs in Ambystoma mexicanum limb regeneration. Developmental biology 68 21539833
2020 Mesenchymal Plasticity Regulated by Prrx1 Drives Aggressive Pancreatic Cancer Biology. Gastroenterology 66 33007300
2016 miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer. Journal of cellular and molecular medicine 60 26820102
2006 Trans-repressive effect of NUP98-PMX1 on PMX1-regulated c-FOS gene through recruitment of histone deacetylase 1 by FG repeats. Cancer research 60 16651408
2012 The transcription factor paired-related homeobox 1 (Prrx1) inhibits adipogenesis by activating transforming growth factor-β (TGFβ) signaling. The Journal of biological chemistry 57 23250756
2022 Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice. Nature genetics 54 36456880
2016 LGR5 Is a Gastric Cancer Stem Cell Marker Associated with Stemness and the EMT Signature Genes NANOG, NANOGP8, PRRX1, TWIST1, and BMI1. PloS one 50 28033430
2021 Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma. Cell death & disease 49 34131109
2011 Identification of the homeobox protein Prx1 (MHox, Prrx-1) as a regulator of osterix expression and mediator of tumor necrosis factor α action in osteoblast differentiation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 49 20683885
2021 Induction and expansion of human PRRX1+ limb-bud-like mesenchymal cells from pluripotent stem cells. Nature biomedical engineering 45 34373601
2014 PRRX1 and PRRX2 distinctively participate in pituitary organogenesis and a cell-supply system. Cell and tissue research 44 24770895
2000 Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome. Mammalian genome : official journal of the International Mammalian Genome Society 42 11063257
2019 PRRX1 Regulates Cellular Phenotype Plasticity and Dormancy of Head and Neck Squamous Cell Carcinoma Through miR-642b-3p. Neoplasia (New York, N.Y.) 40 30622052
2015 PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development. Cell and tissue research 35 25795141
2019 PRRX1 isoforms cooperate with FOXM1 to regulate the DNA damage response in pancreatic cancer cells. Oncogene 34 30705403
2018 gga-mir-133a-3p Regulates Myoblasts Proliferation and Differentiation by Targeting PRRX1. Frontiers in genetics 34 30564268
2017 Diminished PRRX1 Expression Is Associated With Increased Risk of Atrial Fibrillation and Shortening of the Cardiac Action Potential. Circulation. Cardiovascular genetics 33 28974514
2021 RNA binding protein RBMS3 is a common EMT effector that modulates triple-negative breast cancer progression via stabilizing PRRX1 mRNA. Oncogene 31 34608266
2019 Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1. Journal of experimental & clinical cancer research : CR 30 31752959
2015 Down-regualtion of miR-106b induces epithelial-mesenchymal transition but suppresses metastatic colonization by targeting Prrx1 in colorectal cancer. International journal of clinical and experimental pathology 28 26617763
1997 A competitive mechanism of CArG element regulation by YY1 and SRF: implications for assessment of Phox1/MHox transcription factor interactions at CArG elements. DNA and cell biology 28 9174170
2019 The Prrx1 limb enhancer marks an adult subpopulation of injury-responsive dermal fibroblasts. Biology open 27 31278164
2022 Mechanical stimulation promotes enthesis injury repair by mobilizing Prrx1+ cells via ciliary TGF-β signaling. eLife 26 35475783
2020 COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1. Scientific reports 26 33214660
2013 Recurrent agnathia-otocephaly caused by DNA replication slippage in PRRX1. American journal of medical genetics. Part A 26 23444262
2019 PRRX1-induced epithelial-to-mesenchymal transition in salivary adenoid cystic carcinoma activates the metabolic reprogramming of free fatty acids to promote invasion and metastasis. Cell proliferation 23 31657086
2020 Effects of miR-330-3p on Invasion, Migration and EMT of Gastric Cancer Cells by Targeting PRRX1-Mediated Wnt/β-Catenin Signaling Pathway. OncoTargets and therapy 22 32368097
1997 Protein and DNA contact surfaces that mediate the selective action of the Phox1 homeodomain at the c-fos serum response element. Molecular and cellular biology 21 9343429
2021 PRRX1-NCOA1-rearranged fibroblastic tumour: a clinicopathological, immunohistochemical and molecular genetic study of six cases of a potentially under-recognised, distinctive mesenchymal tumour. Histopathology 19 34272753
2011 Agnathia-otocephaly complex: a case report and examination of the OTX2 and PRRX1 genes. Gene 19 22198066
2008 Leukemogenic properties of NUP98-PMX1 are linked to NUP98 and homeodomain sequence functions but not to binding properties of PMX1 to serum response factor. Oncogene 17 18604245
2020 Fatty acid synthase contributes to epithelial-mesenchymal transition and invasion of salivary adenoid cystic carcinoma through PRRX1/Wnt/β-catenin pathway. Journal of cellular and molecular medicine 16 32820613
2023 "PRRX1-rearranged mesenchymal tumors": expanding the immunohistochemical profile and molecular spectrum of a recently described entity with the proposed revision of nomenclature. Virchows Archiv : an international journal of pathology 15 37338620
2021 The Regulatory Role of PRRX1 in Cancer Epithelial-Mesenchymal Transition. OncoTargets and therapy 15 34295164
2020 PRRX1 isoform PRRX1A regulates the stemness phenotype and epithelial-mesenchymal transition (EMT) of cancer stem-like cells (CSCs) derived from non-small cell lung cancer (NSCLC). Translational lung cancer research 15 32676335
2019 Site-Specific Load-Induced Expansion of Sca-1+Prrx1+ and Sca-1-Prrx1+ Cells in Adult Mouse Long Bone Is Attenuated With Age. JBMR plus 15 31667455
2024 Transcription factor Twist1 drives fibroblast activation to promote kidney fibrosis via signaling proteins Prrx1/TNC. Kidney international 14 39181396
2022 Prrx1 promotes resistance to temozolomide by upregulating ABCC1 and inducing vasculogenic mimicry in glioma. American journal of cancer research 13 36119823
2021 PRRX1 deficiency induces mesenchymal-epithelial transition through PITX2/miR-200-dependent SLUG/CTNNB1 regulation in hepatocellular carcinoma. Cancer science 13 33587761
2021 PRRX1 Loss-of-Function Mutations Underlying Familial Atrial Fibrillation. Journal of the American Heart Association 13 34845933
2023 PRRX1+MSCs Enhance Mandibular Regeneration during Distraction Osteogenesis. Journal of dental research 12 37387366
2021 Low PRRX1 expression and high ZEB1 expression are significantly correlated with epithelial-mesenchymal transition and tumor angiogenesis in non-small cell lung cancer. Medicine 12 33530259
2021 The emerging PRRX1-NCOA fibroblastic neoplasm: a combined reappraisal of published tumors and two new cases. Virchows Archiv : an international journal of pathology 12 34647172
2020 PRRX1 promotes malignant properties in human osteosarcoma. Translational oncology 12 33395745
2022 A novel PRRX1 loss-of-function variation contributing to familial atrial fibrillation and congenital patent ductus arteriosus. Genetics and molecular biology 11 35377386
2021 Isolation of PRRX1-positive adult pituitary stem/progenitor cells from the marginal cell layer of the mouse anterior lobe. Stem cell research 11 33561660
2021 Activation of COL11A1 by PRRX1 promotes tumor progression and radioresistance in ovarian cancer. International journal of radiation biology 11 33970764
2021 A Variant Noncoding Region Regulates Prrx1 and Predisposes to Atrial Arrhythmias. Circulation research 11 34092116
2020 The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1. Cell death & disease 11 32811812
2022 Pigmented PRRX1::NCOA1-rearranged fibroblastic tumor: A rare morphologic variant of an emerging mesenchymal tumor. Journal of cutaneous pathology 10 35583270
2022 The paired-related homeobox protein 1 promotes cardiac fibrosis via the Twist1-Prrx1-tenascin-C loop. Cell biology international 10 36273425
2021 PRRX1 promotes lymph node metastasis of gastric cancer by regulating epithelial-mesenchymal transition. Medicine 10 33578599
2017 The role of PRRX1 in the apoptosis of A549 cells induced by cisplatin. American journal of translational research 10 28337269
2017 Loss of PRRX1 induces epithelial-mesenchymal transition and cancer stem cell-like properties in A549 cells. American journal of translational research 10 28469771
2024 PRRX1-OLR1 axis supports CAFs-mediated lung cancer progression and immune suppression. Cancer cell international 9 39010054
2019 Aberrant expression of vasculogenic mimicry, PRRX1, and CIP2A in clear cell renal cell carcinoma and its clinicopathological significance. Medicine 9 31490389
2016 [miR-124 regulates radiosensitivity of colorectal cancer cells by targeting PRRX1]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 9 27578582
2022 Transcription factor paired related homeobox 1 (PRRX1) activates matrix metalloproteinases (MMP)13, which promotes the dextran sulfate sodium-induced inflammation and barrier dysfunction of NCM460 cells. Bioengineered 8 34967278
2023 Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance. Genetics in medicine : official journal of the American College of Medical Genetics 7 37154149
2022 PRRX1 promotes colorectal cancer stemness and chemoresistance via the JAK2/STAT3 axis by targeting IL-6. Journal of gastrointestinal oncology 7 36636075
2021 PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A. Molecular oncology 7 34214250
2019 Transcription Factor prrx1 Promotes Brown Adipose-Derived Stem Cells Differentiation to Sinus Node-Like Cells. DNA and cell biology 7 31545082
2025 Revealing RB1 loss in an emerging entity: report of two cases of PRRX1-rearranged mesenchymal tumours. Journal of clinical pathology 6 38154915
2025 Cardioprotective potential of transcription factor PRRX1 silencing against myocardial ischemia/reperfusion injury by regulating excessive mitophagy and ferroptosis through FKBP5-p38 MAPK axis. Biochimica et biophysica acta. Molecular basis of disease 6 40044064
2024 PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. British journal of cancer 6 38448751
2022 SPOCK1 silencing decreases 5-FU resistance through PRRX1 in colorectal cancer. Pathology, research and practice 6 35462225
2021 Tumor suppressive microRNA-485-5p targets PRRX1 in human skin melanoma cells, regulating epithelial-mesenchymal transition and apoptosis. Cell biology international 6 33620119
2021 LncRNA FEZF1-AS1 promotes colorectal cancer progression through regulating the miR-363-3p/PRRX1 pathway. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 6 34286520
2021 Downregulation of miR-216a-5p and miR-652-3p is associated with growth and invasion by targeting JAK2 and PRRX1 in GH-producing pituitary tumours. Journal of molecular endocrinology 6 34738916
2020 Relationship between PRRX1, circulating tumor cells, and clinicopathological parameter in patients with gastric cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 6 32862590
2018 PRRX1 drives tamoxifen therapy resistance through induction of epithelial-mesenchymal transition in MCF-7 breast cancer cells. International journal of clinical and experimental pathology 6 31938377
2024 PRRX1-fused mesenchymal neoplasm: A novel PRRX1::NCOA1 fusion transcript. Journal of cutaneous pathology 5 38986510
2022 PRRX1/FOXM1 reduces gemcitabin-induced cytotoxicity by regulating autophagy in bladder cancer. Translational andrology and urology 5 36092834
2020 Deletion of α-Synuclein in Prrx1-positive cells causes partial loss of function in the central nervous system (CNS) but does not affect ovariectomy induced bone loss. Bone 5 32417536
2004 [Development of human myeloid leukemia-like phenotype in NUP98-PMX1 transgenic mice]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 5 15182531
2023 ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias. Blood cancer journal 4 36959186
2022 Age-Progressive and Gender-Dependent Bone Phenotype in Mice Lacking Both Ebf1 and Ebf2 in Prrx1-Expressing Mesenchymal Cells. Calcified tissue international 4 35137272
2020 Nicotine inhibits expression of Prrx1 in pituitary stem/progenitor cells through epigenetic regulation, leading to a delayed supply of growth-hormone-producing cells. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 4 32146343
2025 PRRX1-Rearranged Mesenchymal Tumor in a Core Needle Biopsy. International journal of surgical pathology 3 39887195
2024 Reciprocal negative feedback between Prrx1 and miR-140-3p regulates rapid chondrogenesis in the regenerating antler. Cellular & molecular biology letters 3 38643083
2024 LncRNA KIFAP3-5:1 inhibits epithelial-mesenchymal transition of renal tubular cell through PRRX1 in diabetic nephropathy. Cell biology and toxicology 3 38869718
2024 Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer. Life sciences 3 39528080
2023 A PRRX1 Signature Identifies TIM-3 and VISTA as Potential Immune Checkpoint Targets in a Subgroup of Microsatellite Stable Colorectal Cancer Liver Metastases. Cancer research communications 3 36968142
2022 Identification of Surface Antigens That Define Human Pluripotent Stem Cell-Derived PRRX1+Limb-Bud-like Mesenchymal Cells. International journal of molecular sciences 3 35269809
2016 Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma. Journal of pathology and translational medicine 3 27580127
2025 Extracellular Matrix Stiffness Enhancement Promotes Docetaxel Resistance in Prostate Cancer via Inhibition of Apoptosis Mediated by Upregulation of PRRX1. International journal of medical sciences 2 40860778
2024 Prrx1-driven LINC complex disruption in vivo reduces osteoid deposition but not bone quality after voluntary wheel running. bioRxiv : the preprint server for biology 2 37790521
2021 First case report of a NUP98-PMX1 rearrangement in de novo acute myeloid leukemia and literature review. BMC medical genomics 2 34001105
2025 [PRRX1-rearranged fibroblastic tumor: a clinicopathological and molecular analysis of four cases]. Zhonghua bing li xue za zhi = Chinese journal of pathology 1 40159029
2025 PRRX1 Orchestrates Pericyte-Myofibroblast Transition in Pathological Retinal Fibrosis. Investigative ophthalmology & visual science 1 41230906
2025 PEGylated black-phosphorus nanosheet-alginate hydrogels enable local PRRX1 delivery to drive fibroblast reprogramming in intestinal fibrosis. Journal of nanobiotechnology 1 41350883
2024 Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample. Oncology letters 1 38638845