Affinage

HOPX

Homeodomain-only protein · UniProt Q9BPY8

Length
73 aa
Mass
8.3 kDa
Annotated
2026-06-10
69 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOPX is a small, atypical non-DNA-binding homeodomain protein that functions as a transcriptional co-regulator, controlling cell proliferation, differentiation, and survival across cardiac, neural, hematopoietic, epithelial, immune, and tumor contexts (PMID:20833366, PMID:38091997). A core mechanism is its partnership with HDAC2: in the developing heart HOPX recruits and stabilizes HDAC2 to deacetylate the transcription factor GATA4, blunting GATA4-driven cell-cycle gene transactivation and thereby restraining cardiomyocyte proliferation (PMID:20833366), while in acute myeloid leukemia the same HOPX-HDAC2 interaction enforces a differentiation block and drives malignant progression (PMID:39243399). HOPX also represses serum response factor (SRF)-dependent transcription, suppressing estrogen-stimulated c-fos induction in endometrial cells and trophoblast giant-cell differentiation (PMID:19173292, PMID:17576768). In cardiomyocyte commitment and maturation, HOPX integrates niche signals by binding activated SMAD proteins to repress Wnt targets and by controlling enhancer networks that define cardiomyocyte identity downstream of growth and hypertrophic signals (PMID:26113728, PMID:30290179, PMID:38091997). Across stem/progenitor compartments HOPX maintains quiescence and lineage decisions: it limits Wnt/β-catenin signaling to support primitive hematopoiesis and hematopoietic stem cell quiescence via the CXCL12-CXCR4 axis (PMID:28813672, PMID:32533098), regulates dentate-gyrus neural stem cell quiescence through Notch signaling and is necessary and sufficient for basal radial glia generation in neocortex (PMID:26451648, PMID:30266827). As a tumor suppressor, HOPX epigenetically silences SNAIL through enhanced H3K9 deacetylation to block EMT and metastasis, cooperates with GATA6 to limit metastatic competence, and promotes oncogenic Ras-induced senescence (PMID:23707782, PMID:28146149, PMID:25345926, PMID:40804282). HOPX expression is itself controlled epigenetically by promoter methylation (DNMT3B) and CpG silencing, by EZH2-mediated repression, and by upstream transcription factors GRHL3 and KLF4 (PMID:18234960, PMID:32647304, PMID:41660264, PMID:36442813). In immune cells HOPX sustains regulatory T cell function and Th1 persistence by suppressing the AP-1 complex and intrinsic IL-2 and by conferring resistance to Fas-induced apoptosis (PMID:21061432, PMID:20802482, PMID:26170384). More recent work links HOPX to β-catenin stabilization via competitive inhibition of UBA52-mediated ubiquitination and to nuclear translocation that drives NF-κB activation in drug-tolerant persister cells (PMID:42157941, PMID:40352726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 Low

    Establishing HOPX as a small homeodomain protein with differentiation-promoting, tumor-suppressive activity gave the first functional handle on an otherwise uncharacterized gene.

    Evidence Forced expression of NECC1/HOPX in choriocarcinoma lines with xenograft tumorigenesis assay

    PMID:12573257

    Open questions at the time
    • No molecular partner or mechanism defined
    • Single forced-expression study without pathway delineation
  2. 2007 Medium

    Identifying SRF as a functional target answered how HOPX restrains transcription without binding DNA, linking it to lineage decisions in the placenta.

    Evidence Genetic knockout mouse and forced expression in trophoblast stem cells with SRF activity analysis

    PMID:17576768

    Open questions at the time
    • Direct HOPX-SRF binding not biochemically dissected here
    • Generalizability beyond trophoblast unclear
  3. 2010 High

    Discovery of the HOPX-HDAC2 complex deacetylating GATA4 explained at the biochemical level how HOPX suppresses cardiomyocyte proliferation, defining its prototypical co-repressor mechanism.

    Evidence Reciprocal Co-IP, double-knockout mice, and in vitro deacetylation assays on GATA4

    PMID:20833366

    Open questions at the time
    • How HOPX selects GATA4 vs other substrates not defined
    • Structural basis of HDAC2 recruitment unknown
  4. 2010 High

    Demonstrating HOPX requirement in iTreg/Th1 cells extended its role from development to immune tolerance and effector persistence via AP-1 suppression and apoptosis resistance.

    Evidence Hopx-deficient mice, DC-mediated iTreg induction, adoptive transfer and Fas-apoptosis assays

    PMID:20802482 PMID:21061432

    Open questions at the time
    • Mechanism of AP-1 downregulation not resolved
    • Direct transcriptional targets in T cells not mapped
  5. 2013 Medium

    Showing HOPX cooperates with GATA6 to suppress invasion positioned it as a lineage transcription factor limiting metastatic competence in solid tumors.

    Evidence Gain/loss-of-function in lung adenocarcinoma lines with invasion and in vivo metastasis models

    PMID:23707782

    Open questions at the time
    • Direct HOPX-GATA6 physical interaction not established
    • Shared target genes only partially defined
  6. 2015 High

    Linking HOPX to SMAD binding and Wnt repression revealed it as a signaling integrator driving cardiomyocyte commitment, and parallel work tied IL-2 suppression to Treg maintenance.

    Evidence Co-IP of HOPX-SMAD, Wnt reporter assays, lineage tracing; Hopx-deficient pTreg IL-2 measurement in EAE model

    PMID:26113728 PMID:26170384

    Open questions at the time
    • Specific Wnt target genes repressed not enumerated
    • Whether SMAD binding is direct or complex-mediated unresolved
  7. 2015 Medium

    Defining HOPX as a marker and regulator of adult dentate-gyrus NSC quiescence via Notch distinguished hippocampal from ventricular stem cells.

    Evidence Hopx-null mice, BrdU labeling, Notch target gene and NICD analysis

    PMID:26451648

    Open questions at the time
    • How HOPX modulates Notch signaling mechanistically unknown
    • Direct transcriptional targets not identified
  8. 2017 Medium

    ChIP demonstration of H3K9 deacetylation at the SNAIL promoter gave a concrete epigenetic mechanism for HOPX's anti-metastatic function, complemented by Wnt suppression in hematopoiesis.

    Evidence ChIP at SNAIL promoter in NPC cells; HOPX-KO hESC with ATAC-seq and Wnt readout in blood-forming endothelium

    PMID:28146149 PMID:28813672

    Open questions at the time
    • HDAC partner at SNAIL promoter not identified in NPC
    • Whether SNAIL silencing generalizes across tumor types tested separately
  9. 2018 Medium

    Genomic profiling established that HOPX governs enhancer networks and cardiomyocyte maturation downstream of hypertrophic/growth signals, and that it controls basal radial glia abundance in cortex.

    Evidence scRNA-seq and gain/loss-of-function in hPSC-cardiomyocytes; in vivo CRISPR and electroporation for bRGC quantification

    PMID:30266827 PMID:30290179

    Open questions at the time
    • Enhancer recruitment mechanism for a non-DNA-binding protein unresolved
    • Co-factors directing HOPX to specific loci unknown
  10. 2020 Medium

    Conditional hematopoietic knockout connected HOPX to HSC quiescence and reconstitution through the CXCL12-CXCR4 axis, and EZH2 was shown to repress HOPX during BMSC differentiation.

    Evidence Conditional Hopx-KO mice, serial transplantation, transcriptomics; ChIP of EZH2 at HOPX promoter with BMSC gain/loss-of-function

    PMID:32533098 PMID:32647304

    Open questions at the time
    • Whether HOPX directly regulates Cxcl12/Cxcr4 transcription not shown
    • Substrate/target specificity in HSCs undefined
  11. 2022 Medium

    Upstream regulatory architecture was clarified by showing GRHL3 transcriptionally activates HOPX, which then limits Wnt/β-catenin to suppress esophageal carcinoma progression.

    Evidence ChIP-seq for GRHL3 binding at HOPX, conditional Grhl3 mice, patient ESCC validation

    PMID:36442813

    Open questions at the time
    • Mechanism by which HOPX limits Wnt in this context not biochemically defined
  12. 2024 Medium

    Re-demonstration of the HOPX-HDAC2 complex in AML reframed the same molecular interaction as oncogenic, enforcing a differentiation block.

    Evidence Endogenous and exogenous Co-IP with proliferation/apoptosis functional assays in AML cells

    PMID:39243399

    Open questions at the time
    • Target genes/substrates of HOPX-HDAC2 in AML not identified
    • Why the same complex is suppressive in heart but oncogenic in AML unexplained
  13. 2025 Medium

    Recent work uncovered new HOPX behaviors: cytoplasmic-to-nuclear translocation driving NF-κB and repressive histone marks in drug-tolerant persisters, SNAIL suppression in HCC, and DNMT3B methylation controlling HOPX expression.

    Evidence scATAC-seq, CRISPR deletion, subcellular fractionation and NF-κB assays (DTP); forced expression/knockdown in HCC; DNMT3B gain/loss with HOPX rescue in lung cancer

    PMID:40352726 PMID:40804282 PMID:41660264

    Open questions at the time
    • Trigger and machinery for HOPX nuclear translocation undefined
    • How HOPX engages NF-κB mechanistically unknown
  14. 2026 Medium

    Identification of UBA52 as a HOPX partner revealed a post-translational mechanism: HOPX competitively blocks UBA52-mediated β-catenin ubiquitination to stabilize β-catenin in iron-stimulated intestinal stem cells.

    Evidence Co-IP of HOPX-UBA52 and HOPX-β-catenin, ubiquitination assay, Hopx genetic models, high-iron diet

    PMID:42157941

    Open questions at the time
    • Reconciliation with prior reports of HOPX limiting Wnt/β-catenin not addressed
    • Structural basis of competitive binding unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a non-DNA-binding homeodomain protein is recruited to context-specific enhancers and partners (HDAC2, SMAD, SRF, UBA52) to produce opposite outcomes (tumor suppression vs oncogenic persistence) remains unresolved.
  • No structural model of HOPX-partner complexes
  • Determinants of cell-type-specific co-factor selection unknown
  • Mechanism switching HOPX between cytoplasmic and nuclear/repressive roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3
Partners
CTNNB1GATA4GATA6HDAC2SMADSRFUBA52

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 HOPX physically interacts with HDAC2, and this complex mediates deacetylation of the non-histone transcription factor GATA4. HOPX stabilizes the HDAC2-GATA4 interaction, and Hopx/Hdac2-mediated deacetylation of GATA4 impairs its ability to transactivate cell cycle genes, thereby suppressing cardiac myocyte proliferation during embryonic development. Loss of both Hopx and Hdac2 leads to GATA4 hyperacetylation and increased cardiomyocyte proliferation. Co-immunoprecipitation (physical interaction), mouse genetic knockout (double mutant), in vitro deacetylation assays, gene expression analysis of Gata4 target genes Developmental cell High 20833366
2015 HOPX coordinates BMP and Wnt signaling in cardiomyoblasts by physically interacting with activated SMAD proteins (downstream of BMP) to repress Wnt target genes, thereby promoting cardiomyocyte commitment. This mechanism positions HOPX as an integrator of niche signals that inhibits Wnt signaling to drive cardiomyogenesis. Co-immunoprecipitation (HOPX-SMAD interaction), genetic gain- and loss-of-function in vivo, reporter assays for Wnt signaling, lineage tracing Science (New York, N.Y.) High 26113728
2009 HOPX suppresses estrogen-stimulated proliferation in endometrial cancer cells by inhibiting serum response factor (SRF)-dependent transcription. Specifically, forced HOPX expression blocked E2-induced c-fos activation through the serum response element (SRE) of the c-fos promoter, and HOPX knockdown in immortalized endometrial cells accelerated proliferation. Forced expression and RNAi knockdown, SRE luciferase reporter assay, cell proliferation assay, in vivo tumorigenicity assay International journal of cancer Medium 19173292
2007 HOP/NECC1 negatively regulates serum response factor (SRF) transcriptional activity in trophoblasts. Forced expression of SRF in trophoblast stem cells induces differentiation into giant cells, and HOP/NECC1 binding to SRF contributes to restraining giant cell formation and promoting spongiotrophoblast formation. HOP/NECC1-null placenta exhibited excess giant cell layers and reduced spongiotrophoblast. Genetic knockout mouse model, forced expression in trophoblast stem cell lines, differentiation assays, analysis of SRF transcriptional activity The Journal of biological chemistry Medium 17576768
2010 HOPX is required for the survival and persistence of Th1 effector/memory cells by regulating genes involved in apoptosis and making them refractory to Fas-induced apoptosis. HOPX expression is induced by T-bet and upregulated upon repeated antigenic restimulation; Hopx-deficient murine Th1 cells fail to persist in vivo and cannot induce chronic colitis or arthritis. Adoptive transfer of Hopx-deficient Th1 cells in vivo, murine colitis and arthritis models, apoptosis assays (Fas-induced), gene expression profiling European journal of immunology Medium 21061432
2010 HOPX (Hop) is required for the function of induced regulatory T cells (iTreg) generated by peripheral dendritic cells. Hopx-sufficient iTreg cells downregulate AP-1 complex expression and suppress other T cells, whereas Hopx-deficient iTreg cells show high AP-1 expression, proliferate abnormally, and fail to mediate T cell unresponsiveness to antigen rechallenge in vivo. Genetic loss-of-function (Hopx-deficient mice), DC-mediated iTreg induction assay, antigen rechallenge model in vivo, AP-1 expression analysis Nature immunology High 20802482
2015 Hopx inhibits intrinsic IL-2 expression in peripherally induced regulatory T cells (pTregs) following antigenic rechallenge. In the absence of Hopx, increased IL-2 levels lead to death and decreased numbers of pTregs. Hopx+ pTregs converted by DCs are indispensable to sustain tolerance that prevents autoimmune responses in experimental encephalomyelitis. Genetic Hopx-deficiency in T cells, adoptive transfer, IL-2 measurement, EAE model in vivo Journal of immunology (Baltimore, Md. : 1950) Medium 26170384
2013 HOPX and GATA6 cooperatively limit metastatic competence of lung adenocarcinoma cells by modulating overlapping alveolar differentiation and invasogenic target genes. Functional experiments showed that these two lineage transcription factors act together to suppress invasion and metastasis. Gain- and loss-of-function in lung cancer cell lines, invasion assays, gene expression analysis, in vivo metastasis models Cancer cell Medium 23707782
2017 HOPX acts as a tumor suppressor in nasopharyngeal carcinoma by epigenetically silencing SNAIL transcription through enhancement of histone H3K9 deacetylation at the SNAIL promoter. Restoring HOPX expression suppresses NPC cell metastasis and enhances chemosensitivity. Forced expression and knockdown in NPC cell lines, chromatin immunoprecipitation (H3K9 deacetylation at SNAIL promoter), in vitro migration/invasion assays, in vivo metastasis models Nature communications Medium 28146149
2014 HOPX exerts tumor-suppressive activity in lung cancer cells through oncogenic Ras-induced cellular senescence via activation of the MAPK pathway, leading to decreased MDM2 and increased p21. Knockdown of HOPX by siRNA reduced Ras activity, inactivated the MAPK pathway, decreased p21, and reduced senescence. Stable transfection with HOPX expression vector, siRNA knockdown, Ras activity assay, MAPK signaling analysis, senescence assays (SA-β-gal), p21/MDM2 western blot The Journal of pathology Medium 25345926
2015 Hopx is specifically expressed in radial glia-like (RGL) neural stem cells of the adult dentate gyrus (DG) but not in the lateral ventricle proliferative zone, distinguishing hippocampal NSCs from lateral ventricle NSCs. Hopx-null NSCs exhibit enhanced neurogenesis with increased BrdU+ cells and reduced quiescent Sox2+ NSCs. Hopx regulates hippocampal NSC quiescence at least partly by modulating Notch signaling (reduced Hes1, Hey2, and NICD in Hopx-null DG). Lineage tracing, genetic knockout (Hopx-null mice), BrdU labeling, doublecortin immunostaining, Notch target gene expression analysis, cleaved Notch1 (NICD) immunostaining Stem cell research Medium 26451648
2018 HOPX is required for cardiomyocyte maturation during hPSC cardiac differentiation. Loss-of-function and gain-of-function experiments showed that hypertrophic signaling activates HOPX, which in turn activates downstream gene programs governing late-stage cardiomyocyte maturation. HOPX controls enhancer networks and cardiac gene programs associated with cardiomyocyte identity. Single-cell transcriptomics, genetic gain- and loss-of-function in hPSC-derived cardiomyocytes, gene expression profiling Cell stem cell Medium 30290179
2023 HOPX (a non-DNA-binding homeodomain protein) interacts with and controls cardiac gene enhancer networks in cardiomyocytes. Upstream cell growth and proliferation signals control HOPX transcription, which regulates downstream gene programs underpinning cardiomyocyte identity and function. HOPX-regulated programs were validated in vitro, in organoids, and in zebrafish regeneration models. Genetic loss-of-function in hiPSC-derived cardiomyocytes, perturbation studies, ATAC-seq/ChIP-seq for enhancer analysis, zebrafish regeneration model, cardiac organoids Developmental cell High 38091997
2017 HOPX regulates primitive hematopoiesis by suppressing Wnt/β-catenin signaling in blood-forming endothelial cells. Using HOPX reporter and knockout hESCs, loss of HOPX markedly reduces primitive hematopoiesis while not affecting endothelial fate specification. HOPX reporter and knockout hESC lines, chromatin accessibility (ATAC-seq), transcriptional profiling, hematopoietic differentiation assays, Wnt/β-catenin signaling readout Cell reports Medium 28813672
2020 Hematopoietic-specific knockout of Hopx in mice leads to decreased HSC reconstitution ability, reduced HSC quiescence signatures, and downregulation of the Cxcl12-Cxcr4 axis. Hopx-/- HSCs show decreased CXCL12 and CXCR4 expression, implicating this pathway as a mechanism by which Hopx maintains HSC quiescence. Conditional hematopoietic Hopx knockout mouse model, serial transplantation assay, transcriptomic analysis of HSCs, CXCL12/CXCR4 expression measurement, AML model (MN1 overexpression) Oncogene Medium 32533098
2018 Hopx is required for basal radial glial cell (bRGC) abundance in the developing mouse neocortex. Disruption of Hopx expression in mouse embryonic medial neocortex reduces bRGC numbers, and forced Hopx expression in lateral neocortex increases bRGC abundance to levels seen in gyrencephalic neocortex, demonstrating that Hopx is both necessary and sufficient for bRGC generation. Genetic disruption (CRISPR/electroporation in vivo), forced expression (in utero electroporation), quantitative histology of bRGC populations, lineage tracing Development (Cambridge, England) Medium 30266827
2010 HOPX expression in human keratinocytes is induced through the PKC signaling pathway (activated by PMA), but not by the demethylating agent 5-aza-dC, suggesting its regulation is not associated with DNA methylation in this cell type. Knockdown of HOPX by RNAi increases differentiation markers (involucrin and loricrin), while forced exogenous HOPX downregulates differentiation marker genes in HaCaT cells. RNAi knockdown, forced expression, PKC pathway inhibition, differentiation marker gene expression (involucrin, loricrin), calcium-triggered differentiation assay European journal of cell biology Medium 20226564
2003 NECC1/HOPX (also called LAGY) encodes a small 73 amino acid homeodomain protein. Transfection of NECC1 into choriocarcinoma cell lines induces CSH1 (chorionic somatomammotropin hormone 1) expression and suppresses in vivo tumorigenesis, suggesting differentiation toward syncytiotrophoblasts. Transfection/forced expression in choriocarcinoma cell lines, in vivo xenograft tumorigenesis assay, expression profiling Genomics Low 12573257
2008 HOP/OB1/NECC1 (HOPX) has two promoters (A and B) encoding two isoforms (HOPα and HOPβ). HOPβ silencing is associated with dense CpG island methylation at promoter B in esophageal squamous cell carcinoma, and forced HOP expression suppresses tumorigenesis in soft agar assays in four different squamous cell carcinoma cell lines. RNA interference knockdown of HOP restores the oncogenic phenotype. Methylation-specific PCR (TaqMan), demethylating agent treatment (5-aza-dCR + TSA), forced expression and RNAi knockdown, soft agar colony formation assay Molecular cancer research : MCR Medium 18234960
2020 EZH2 directly binds to the HOPX promoter region during normal growth and osteogenic differentiation (but not adipogenic conditions), thereby repressing HOPX. HOPX promotes BMSC proliferation and inhibits adipogenesis by suppressing adipogenic pathway genes (ADIPOQ, FABP4, PLIN1, PLIN4), as shown by gain- and loss-of-function studies and RNA-seq. ChIP (EZH2 binding to HOPX promoter), HOPX knockdown and overexpression in BMSCs, RNA-seq during adipogenesis, differentiation assays Scientific reports Medium 32647304
2016 HOPX and KLF4 cooperate to activate claudin 4, 7, and 15 expression during colonic epithelial differentiation, as shown by correlation analysis, in vitro confirmatory methods, and chromatin immunoprecipitation identifying the Hopx/Klf4 cascade as a regulator of barrier gene expression. Gene expression microarray/correlation analysis, in vitro confirmatory assays, chromatin immunoprecipitation (ChIP), conditional knockout mice for validation Tissue barriers Low 27583195
2024 HOPX physically interacts with HDAC2 in AML cells (confirmed by endogenous and exogenous co-immunoprecipitation), and this HOPX-HDAC2 interaction induces differentiation blockage and malignant progression in AML. Low HOPX expression represses AML cell proliferation, anti-apoptotic activity, and differentiation blockage. Endogenous and exogenous Co-immunoprecipitation, flow cytometry (proliferation and apoptosis), MTT assay, bioinformatics analysis Hematological oncology Medium 39243399
2025 In lung cancer drug-tolerant persister (DTP) cells, HOPX undergoes cytoplasmic-to-nuclear translocation upon targeted therapy treatment. Nuclear HOPX regulates NF-κB activation and repressive histone modifications. HOPX deletion significantly delays DTP regrowth, identifying HOPX as a regulator of DTP persistence through epigenetic and NF-κB-dependent mechanisms. scATAC-seq, HOPX deletion (CRISPR), subcellular fractionation/immunofluorescence for nuclear translocation, NF-κB activity assays, histone modification analysis, in vitro DTP regrowth assay iScience Medium 40352726
2021 Hopx plays a critical role in epigenetic regulation through histone deacetylation in cardiomyocytes treated with antiretroviral drugs (ARVs). HOPX expression is significantly increased in ARV-treated cardiomyocytes and HIV patient heart tissue. HDAC inhibitor Trichostatin A restores histone 3 acetylation in the presence of ARVs, and HOPX is identified as mediating cellular hypertrophy via histone deacetylation. RNA-sequencing of ARV-treated neonatal rat cardiomyocytes, HDAC inhibitor rescue experiment (Trichostatin A), histone acetylation western blot, validation in HIV patient cardiac tissue Cells Low 34943964
2025 Iron released from radiotherapy-induced tumor cell death triggers a Stat3-dependent pro-survival program in neighboring Hopx+ quiescent cancer stem cells, causing their activation. Activated Hopx+ cancer stem cells antagonize ferroptosis (which should be caused by iron overload) through inhibition of de novo lipid synthesis. Lineage-tracing (HopxCreERT2;RosatdTomato mice and organoids), BrdU pulse-chase, cell cycle analysis, apoptosis/necroptosis blockade experiments, human rectal cancer organoids and PDX models Journal of advanced research Medium 41325838
2026 HOPX stabilizes β-catenin protein by directly inhibiting the interaction of β-catenin with UBA52, which targets β-catenin for ubiquitination-mediated degradation. High iron diet activates Wnt/β-catenin signaling in Hopx+ intestinal stem cells in a Hopx-dependent manner through this competitive binding mechanism. Co-immunoprecipitation (HOPX-UBA52 and HOPX-β-catenin interaction), ubiquitination assay, Hopx genetic models, Wnt/β-catenin signaling assays, high-iron diet mouse model International journal of biological sciences Medium 42157941
2025 DNMT3B directly methylates the HOPX promoter, downregulating HOPX expression in lung cancer cells. DNMT inhibitor SGI-1027 upregulates HOPX, and HOPX knockdown partially recovers the malignant phenotypes (proliferation, migration, invasion) suppressed by DNMT3B knockdown or SGI-1027 treatment, placing HOPX downstream of DNMT3B-mediated DNA methylation. DNMT3B overexpression and knockdown, DNMT inhibitor (SGI-1027) treatment, methylation analysis of HOPX promoter, HOPX knockdown rescue experiment, in vitro and in vivo functional assays iScience Medium 41660264
2025 HOPX regulates hepatocellular carcinoma invasion and migration by suppressing SNAIL expression, thereby inhibiting epithelial-to-mesenchymal transition (EMT). HOPX inhibition of SNAIL was required for HOPX's metastasis-inhibitory activity in in vitro and in vivo HCC models. HOPX forced expression and knockdown, invasion/migration assays, SNAIL protein expression analysis, in vivo HCC metastasis mouse model, EMT marker analysis Scientific reports Medium 40804282
2022 GRHL3 transcriptionally regulates HOPX expression in the esophageal epithelium (ChIP-seq confirmed GRHL3 binding to the HOPX locus), and HOPX in turn limits Wnt/β-catenin signaling. Loss of GRHL3 reduces HOPX expression and increases Wnt/β-catenin activity, driving esophageal squamous cell carcinoma progression. ChIP-seq (GRHL3 binding to HOPX), conditional Grhl3 deletion in mice, RNA-seq, immunohistochemistry, Wnt/β-catenin pathway analysis, patient-derived ESCC validation Cellular and molecular gastroenterology and hepatology Medium 36442813
2024 HOPX, operating downstream of GPR109A (activated by butyrate from gut microbiota), enhances CD8+ T cell cytotoxic killing of gastric cancer cells. GPR109A knockout significantly weakened butyrate's enhancement of CD8+ T cell function, and HOPX acted downstream in this GPR109A/HOPX axis. GPR109A knockout mouse model, butyrate supplementation during gastric cancer induction, co-culture of GC cells with CD8+ T cells or CAR-T cells, in vivo tumor-bearing studies, IFN-γ measurement Gut microbes Low 38319728

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nature communications 236 25865356
2018 Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation. Cell stem cell 198 30290179
2010 Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Developmental cell 125 20833366
2013 Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer cell 124 23707782
2015 HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts. Science (New York, N.Y.) 119 26113728
2017 HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma. Nature communications 98 28146149
2024 Gut microbiota modulate CD8+ T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX. Gut microbes 94 38319728
2018 A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex. Development (Cambridge, England) 70 30266827
2013 Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells. Development (Cambridge, England) 66 23487314
2010 Persistence of effector memory Th1 cells is regulated by Hopx. European journal of immunology 61 21061432
2012 Epigenetic silencing of HOPX promotes cancer progression in colorectal cancer. Neoplasia (New York, N.Y.) 60 22904674
2019 The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts. Nature metabolism 57 32694877
2010 The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness. Nature immunology 50 20802482
2009 Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor. International journal of cancer 46 19173292
2008 HOP/OB1/NECC1 promoter DNA is frequently hypermethylated and involved in tumorigenic ability in esophageal squamous cell carcinoma. Molecular cancer research : MCR 46 18234960
2007 The HopX (AvrPphE) family of Pseudomonas syringae type III effectors require a catalytic triad and a novel N-terminal domain for function. Molecular plant-microbe interactions : MPMI 46 17427805
2015 Hopx distinguishes hippocampal from lateral ventricle neural stem cells. Stem cell research 42 26451648
2014 HOPX is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer. The Journal of pathology 42 25345926
2015 Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression. Journal of immunology (Baltimore, Md. : 1950) 40 26170384
2018 Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis. Scientific reports 39 30154568
2012 Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis. BMC cancer 39 22958219
2016 HOPX: The Unusual Homeodomain-Containing Protein. The Journal of investigative dermatology 38 27017330
2003 NECC1, a candidate choriocarcinoma suppressor gene that encodes a homeodomain consensus motif. Genomics 38 12573257
2003 Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer. Oncology 37 12759545
2017 Chromatin and Transcriptional Analysis of Mesoderm Progenitor Cells Identifies HOPX as a Regulator of Primitive Hematopoiesis. Cell reports 33 28813672
2018 HOPX Defines Heterogeneity of Postnatal Subventricular Zone Neural Stem Cells. Stem cell reports 32 30174314
2013 The homeobox only protein homeobox (HOPX) and colorectal cancer. International journal of molecular sciences 32 24287901
2010 Expression of the homeobox gene, HOPX, is modulated by cell differentiation in human keratinocytes and is involved in the expression of differentiation markers. European journal of cell biology 31 20226564
2016 HOPX functions as a tumour suppressor in head and neck cancer. Scientific reports 30 27934959
2007 HOP/NECC1, a novel regulator of mouse trophoblast differentiation. The Journal of biological chemistry 30 17576768
2016 Epigenetic silencing of HOPX contributes to cancer aggressiveness in breast cancer. Cancer letters 27 27756570
2021 HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia. American journal of physiology. Gastrointestinal and liver physiology 26 34549599
2020 The role of HOPX in normal tissues and tumor progression. Bioscience reports 23 31934721
2020 Knock-out of Hopx disrupts stemness and quiescence of hematopoietic stem cells in mice. Oncogene 21 32533098
2019 ΜicroRNA‑421 promotes the progression of non‑small cell lung cancer by targeting HOPX and regulating the Wnt/β‑catenin signaling pathway. Molecular medicine reports 21 31115507
2020 HOPX regulates bone marrow-derived mesenchymal stromal cell fate determination via suppression of adipogenic gene pathways. Scientific reports 18 32647304
2013 Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis. Molecular cancer research : MCR 18 23938949
2022 HOPX: A Unique Homeodomain Protein in Development and Tumor Suppression. Cancers 17 35681746
2016 Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-α cascades. Tissue barriers 17 27583195
2011 Methylation of the homeobox gene, HOPX, is frequently detected in poorly differentiated colorectal cancer. Anticancer research 16 21868534
2022 Roles of Hopx in the differentiation and functions of immune cells. European journal of cell biology 15 35636259
2023 HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function. Developmental cell 13 38091997
2012 The Golgi-associated long coiled-coil protein NECC1 participates in the control of the regulated secretory pathway in PC12 cells. The Biochemical journal 12 22250954
2018 ATX-MS-1467 Induces Long-Term Tolerance to Myelin Basic Protein in (DR2 × Ob1)F1 Mice by Induction of IL-10-Secreting iTregs. Neurology and therapy 11 29542041
2023 HOPX is a tumor-suppressive biomarker that corresponds to T cell infiltration in skin cutaneous melanoma. Cancer cell international 10 37344870
2022 Identification of a Novel GRHL3/HOPX/Wnt/β-Catenin Proto-oncogenic Axis in Squamous Cell Carcinoma of the Esophagus. Cellular and molecular gastroenterology and hepatology 9 36442813
2020 HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle Arrest in Breast Cancer. OncoTargets and therapy 9 32606804
2021 HOPX Exhibits Oncogenic Activity during Squamous Skin Carcinogenesis. The Journal of investigative dermatology 8 33845078
2023 The HOPX and BLBP landscape and gliogenic regions in developing human brain. Journal of anatomy 7 36794762
2022 Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma. Veterinary pathology 7 35220825
2018 HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance. Endocrine connections 7 30400039
2014 Association between non-coding polymorphisms of HOPX gene and syncope in hypertrophic cardiomyopathy. Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology 5 25036325
2025 Paracrine iron activates Hopx+ rectal cancer stem cells to display radioresistance. Journal of advanced research 4 41325838
2022 The cortical hem lacks stem cell potential despite expressing SOX9 and HOPX. Developmental neurobiology 4 36067402
2021 Landscape of Hopx expression in cells of the immune system. Heliyon 4 34805566
2021 HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy. Cells 4 34943964
2025 Epigenomic analysis identifies DTP subpopulation using HOPX to develop targeted therapy resistance in lung adenocarcinoma. iScience 3 40352726
2019 Prediction of onset of remnant gastric cancer by promoter DNA methylation of CDO1/HOPX/Reprimo/E-cadherin. Oncotarget 3 31069006
2025 HOPX regulates the invasion and migration abilities of hepatocellular carcinoma by targeting SNAIL. Scientific reports 2 40804282
2024 Research on the mechanism of HOPX-HDAC2 interaction inducing differentiation blockage in acute myeloid leukemia. Hematological oncology 2 39243399
2024 HOPX as a tumour-suppressive protein in T-cell acute lymphoblastic leukaemia. British journal of haematology 2 39737712
2008 Isolation and pathogenic characterization of an OB1 variant of Babesia rodhaini which has a glycophorin A-independent pathway to murine red blood cells. Veterinary parasitology 1 19084340
2026 A microbiota-IPA axis facilitates intestinal stem cell-mediated regeneration in colitis through a Hopx-associated program. Nature communications 0 41741429
2026 Hopx(+) optic nerve head-astrocytes counter neuronal stress and glaucoma damage. Proceedings of the National Academy of Sciences of the United States of America 0 42044330
2026 Competitive Binding of UBA52 and HOPX Modulates β-catenin Stability in Colorectal Cancer in the Context of High-Iron Intake. International journal of biological sciences 0 42157941
2026 HOPX is required for the generation of umbilical cord blood-derived memory-like NK cells induced by three cytokines. Frontiers in immunology 0 42220529
2025 Beyond Tumor Suppression: The Multifaceted Functions of HOPX in Tissue Differentiation, Metabolism, and Immunity. Cells 0 41227363
2025 DNMT3b promotes proliferation and invasion by mediating HOPX DNA methylation in lung cancer. iScience 0 41660264
2019 All Roads Lead to Rome: Hippocampal Stem Cells Hop(x) the Continuous Way. Cell stem cell 0 31051131

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