Affinage

HOXB13

Homeobox protein Hox-B13 · UniProt Q92826

Length
284 aa
Mass
30.7 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 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

HOXB13 is a homeodomain transcription factor that functions as a context-dependent regulator of androgen receptor (AR) signaling and a developmental determinant of caudal and prostate tissues (PMID:19917249, PMID:12679105, PMID:12668621). In prostate cells it physically associates with the AR DNA-binding domain, repressing classical ARE-driven transcription while conferring androgen responsiveness to promoters bearing HOXB13-response elements, and it can act as a non-DNA-binding repressor that does not disturb AR nuclear translocation (PMID:19917249, PMID:15604291, PMID:21267402). In castration-resistant prostate cancer it serves as a pioneer factor for the constitutively active AR-V7 splice variant, being universally required for and physically interacting with AR-V7 to open chromatin and activate target oncogenes (PMID:29844167). HOXB13 recruits HDAC3 to lipogenic enhancers to deacetylate histones and suppress fatty acid synthase, an interaction abolished by the cancer-predisposing G84E mutation, which causes lipid accumulation and metastasis (PMID:35468964). Its own chromatin engagement and lineage program are tuned by CBP/p300-mediated acetylation at K13, which establishes tumor-specific super-enhancers driving AR, ACK1 and angiogenesis genes (PMID:35849143). HOXB13 also operates as a cofactor of MEIS1, with the two factors co-regulating proteoglycans such as decorin to mediate MEIS1 tumor suppression, and calcineurin-dependent dephosphorylation at S204 controls its nuclear localization and cell-cycle arrest in postnatal cardiomyocytes (PMID:32499640, PMID:32553107). Across colorectal and prostate contexts HOXB13 suppresses growth by destabilizing TCF-4 and inhibiting beta-catenin/TCF transcriptional output and downstream c-myc and cyclin D1 (PMID:15126340, PMID:15928669). HOXB13 expression is itself set by a FOXA1-bound prostate-specific enhancer and silenced by YY1-HDAC4 and EZH2-DNMT3b epigenetic complexes (PMID:20018680, PMID:19013255, PMID:22808286). The prostate cancer risk SNP rs339331 lies within a functional HOXB13-binding enhancer whose risk allele increases HOXB13 binding and RFX6 expression (PMID:24390282).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Establishing HOXB13's native developmental function showed it restrains proliferation and promotes apoptosis in caudal tissues and is required for prostate epithelial differentiation, defining its baseline biology before its cancer roles were dissected.

    Evidence Hoxb13 knockout and Hoxb13/Hoxd13 double-mutant mice with histology, reporter expression mapping, and secretory marker analysis

    PMID:12668621 PMID:12679105

    Open questions at the time
    • Molecular targets mediating proliferation/apoptosis control in the tail bud not identified
    • Mechanism of redundancy with Hoxd13 in prostate morphogenesis unresolved
  2. 2004 High

    The first demonstration that HOXB13 physically binds AR and suppresses hormone-driven AR transcription and prostate cancer cell growth established it as a direct AR-pathway modulator.

    Evidence Co-IP, reporter assays, and overexpression/knockdown with PSA and growth readouts in LNCaP cells

    PMID:15604291

    Open questions at the time
    • Interaction surface on AR not mapped at this stage
    • Whether repression requires HOXB13 DNA binding unresolved
  3. 2004 Medium

    Linking HOXB13 to TCF-4/beta-catenin suppression revealed a growth-arrest mechanism independent of AR, explaining its tumor-suppressive behavior in AR-negative contexts.

    Evidence Forced expression in PC3 cells, TCF-4 reporter, western blot for c-myc/cyclin D1, in vitro and in vivo growth assays

    PMID:15126340

    Open questions at the time
    • Direct mechanism by which HOXB13 lowers TCF-4 not defined
    • Whether effect is transcriptional or post-translational at this stage unclear
  4. 2009 High

    Mapping the AR-DNA-binding-domain interaction and defining HOXB13-response elements showed HOXB13 both represses ARE genes and redirects AR to a distinct cis-regulatory program, refining its dual transcriptional role.

    Evidence Co-IP mapping to AR DBD, reporter assays, and siRNA knockdown with phenotypic readouts in prostate cancer cells

    PMID:19917249

    Open questions at the time
    • Genome-wide scope of HOXB13/AR co-regulation not established
    • Structural basis of the DBD interaction not resolved
  5. 2009 High

    Identifying a FOXA1-bound enhancer required for prostate-specific Hoxb13 transcription explained how HOXB13 expression is restricted to prostate lineage.

    Evidence BAC reporter deletion analysis in transgenic mice and FOXA1 ChIP in human prostate cancer cells

    PMID:20018680

    Open questions at the time
    • Other lineage factors acting at this enhancer not identified
    • Regulation in non-prostate HOXB13-expressing tissues not addressed
  6. 2008 Medium

    Showing YY1-HDAC4 complex recruitment to the HOXB13 promoter identified an epigenetic mechanism silencing HOXB13 in AR-negative prostate cancer.

    Evidence Co-IP for HDAC4-YY1, ChIP at the promoter, promoter mutagenesis reporters, and HDAC inhibitor treatment

    PMID:19013255

    Open questions at the time
    • Signals that trigger YY1-HDAC4 recruitment unknown
    • Relationship to other silencing routes not integrated
  7. 2012 Medium

    Demonstrating EZH2-DNMT3b co-recruitment and DNA/histone methylation at the HOXB13 promoter, reversible by ATRA, expanded the epigenetic silencing repertoire and offered a route to reactivation.

    Evidence ChIP for EZH2/DNMT3b, Co-IP for their interaction, and ATRA treatment with bisulfite methylation analysis

    PMID:22808286

    Open questions at the time
    • Context determining EZH2-DNMT3b versus YY1-HDAC4 silencing not defined
    • In vivo relevance of ATRA reactivation untested
  8. 2014 High

    Connecting the rs339331 prostate cancer risk SNP to a functional HOXB13 binding site provided a direct genetic-mechanistic link between HOXB13 cistrome and inherited disease risk via allele-specific RFX6 regulation.

    Evidence HOXB13 ChIP-seq, allele-specific reporter assays, and knockdown with RFX6 readout

    PMID:24390282

    Open questions at the time
    • Functional role of RFX6 in tumorigenesis not established here
    • Whether other risk loci are similarly HOXB13-dependent unknown
  9. 2018 High

    Defining HOXB13 as a pioneer factor for AR-V7 explained how androgen-independent AR signaling is maintained in CRPC, recasting HOXB13 from AR repressor to enabler of constitutive AR variant activity.

    Evidence ChIP-exo in CRPC cells and patient tissues, Co-IP, and HOXB13 silencing with cistrome and growth readouts

    PMID:29844167

    Open questions at the time
    • Determinants switching HOXB13 between AR repression and AR-V7 pioneering not defined
    • Structural basis of chromatin opening not resolved
  10. 2020 High

    Identifying HOXB13 as a MEIS1 cofactor and the S204 dephosphorylation switch unified its roles as a cell-cycle and tumor-suppression effector across cardiomyocytes and prostate cancer.

    Evidence Cardiomyocyte-specific knockout mice with ChIP-seq and phosphatase assays; CRISPR HOXB13 deletion with ChIP-seq/RNA-seq and xenografts for MEIS1 dependence

    PMID:32499640 PMID:32553107

    Open questions at the time
    • Upstream kinase phosphorylating S204 not identified
    • Whether the MEIS1-HOXB13 module operates in normal prostate not addressed
  11. 2022 High

    Characterizing the HOXB13-HDAC3 lipogenic axis and the K13 acetylation mark provided a direct biochemical explanation for how the G84E mutation predisposes to prostate cancer and how HOXB13 establishes oncogenic super-enhancers.

    Evidence Co-IP, ChIP-seq, histone deacetylation and mass-spectrometry PTM assays, isogenic G84E and K13A mutants, and xenograft models

    PMID:35468964 PMID:35849143

    Open questions at the time
    • Interplay between K13 acetylation and HDAC3 recruitment not jointly tested
    • Whether G84E also alters K13 acetylation unknown
  12. 2018 Medium

    Post-translational stabilization (HBXIP-driven K277 acetylation blocking chaperone-mediated autophagy) and BRD4-driven transcription identified two routes that elevate HOXB13 abundance in cancer.

    Evidence Co-IP, ChIP, K277 acetylation mutagenesis, and BRD4 genetic/pharmacological disruption with expression and viability readouts

    PMID:29471853 PMID:30242092

    Open questions at the time
    • Relative contribution of stability versus transcription to HOXB13 levels in vivo unclear
    • Generality of K277-CMA control across tissues untested
  13. 2020 Medium

    Demonstrating FTO/m6A control of HOXB13 mRNA stability added a post-transcriptional layer linking HOXB13 abundance to WNT-driven metastasis.

    Evidence MeRIP-seq, FTO and YTHDF2 manipulation with mRNA stability assays, and in vivo metastasis model with WNT inhibitor rescue

    PMID:33103587

    Open questions at the time
    • Single-context (endometrial) finding; prostate relevance not tested
    • Direct demonstration of YTHDF2-mediated decay limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HOXB13 is molecularly switched between tumor-suppressive (AR repression, TCF-4 destabilization, lipogenic suppression) and oncogenic (AR-V7 pioneering, super-enhancer activation, metastasis) programs in a single cell remains unresolved.
  • No structural model of HOXB13 on chromatin or in AR/AR-V7/MEIS1 complexes
  • Determinants integrating K13/K277 acetylation and S204 phosphorylation into a unified regulatory logic unknown
  • Cause of context-dependent cytoplasmic versus nuclear localization not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1266738 Developmental Biology 2
Partners
ALX4ARCBP/P300HBXIPHDAC3MEIS1

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 HOXB13 physically interacts with the DNA-binding domain of the androgen receptor (AR) and inhibits transcription of genes containing an androgen-response element (ARE), while the AR:HOXB13 complex confers androgen responsiveness to promoters containing a specific HOXB13-response element; HOXB13 and AR also synergize to enhance transcription of genes with a HOX element juxtaposed to an ARE. Co-immunoprecipitation, reporter transcription assay, siRNA knockdown with proliferation/migration/lipogenesis readouts in prostate cancer cells Molecular cell High 19917249
2004 HOXB13 physically interacts with AR and suppresses hormone-mediated AR transcriptional activity in a dose-responsive manner; overexpression of HOXB13 suppresses androgen-stimulated PSA expression and inhibits LNCaP prostate cancer cell growth in an AR-dependent manner. Co-immunoprecipitation, reporter transcription assay, HOXB13 overexpression/knockdown with PSA expression and cell growth readouts Cancer research High 15604291
2004 HOXB13 suppresses growth of PC3 prostate cancer cells through G1 cell cycle arrest by negatively regulating TCF-4 protein expression and downstream targets c-myc and cyclin D1, inhibiting beta-catenin/TCF-mediated transcriptional activity. Forced HOXB13 expression in HOXB13-negative cells, TCF-4 reporter gene assay, western blot for TCF-4/c-myc/cyclin D1, in vitro and in vivo growth assays Cancer research Medium 15126340
2010 HOXB13 co-localizes with AR in prostate cancer cells and suppresses androgen-stimulated AR activity by interacting with AR; HOXB13 does not bind to AR-responsive elements nor disturb nuclear translocation of AR, acting instead as a non-DNA-binding transcriptional repressor. Co-immunoprecipitation, reporter assay, immunofluorescence co-localization, immunohistochemistry on prostate cancer specimens Anatomy & cell biology Medium 21267402
2010 In androgen-free conditions, HOXB13 promotes LNCaP prostate cancer cell proliferation through activation of RB-E2F signaling by inhibiting p21waf expression. HOXB13 induction/suppression in LNCaP cells, cell proliferation assays, western blot for p21waf and E2F targets Molecular cancer Medium 20504375
2013 HOXB13 upregulates ZnT zinc output transporters in prostate cancer cells, lowering intracellular zinc concentrations, which reduces IκBα and stimulates nuclear translocation of RelA/p65 to activate NF-κB signaling and promote cell invasion and metastasis. DNA microarray, zinc concentration measurement, NF-κB reporter, siRNA knockdown of ZnT4, orthotopic mouse metastasis model Oncogene Medium 24096478
2013 HOXB13 confers tamoxifen resistance in ER-positive breast cancer by directly downregulating ERα transcription, and transcriptionally upregulates IL-6 to activate the mTOR pathway via STAT3 phosphorylation, promoting cell proliferation and fibroblast recruitment. HOXB13 overexpression/knockdown, ChIP, reporter assays, xenograft models, mTOR inhibitor rescue experiments Cancer research High 23832664
2018 HOXB13 acts as a pioneer factor for AR splice variant AR-V7 in castration-resistant prostate cancer (CRPC): HoxB13 is universally required for and co-localizes with AR-V7 binding to open chromatin across CRPC genomes, pioneers AR-V7 binding through direct physical interaction, and collaborates with AR-V7 to up-regulate target oncogenes. ChIP-exo in CRPC cells and patient tissues, Co-IP for physical interaction, HOXB13 silencing with cell growth and AR-V7 cistrome readouts Proceedings of the National Academy of Sciences of the United States of America High 29844167
2020 HOXB13 acts as a cofactor of MEIS1 in postnatal cardiomyocytes to regulate cell cycle arrest; calcineurin dephosphorylates HOXB13 at serine-204, causing its nuclear localization and cell cycle arrest; cardiomyocyte-specific deletion of Hoxb13 extends the postnatal window of cardiomyocyte proliferation and reactivates the adult cardiomyocyte cell cycle. Cardiomyocyte-specific knockout mice, double Meis1-Hoxb13 knockout, ChIP-seq, echocardiography/MRI, phosphatase assay identifying calcineurin-mediated dephosphorylation of Ser204 Nature High 32499640
2022 HOXB13 interacts with histone deacetylase HDAC3 and recruits it to lipogenic enhancers to catalyze histone deacetylation and suppress lipogenic regulators such as fatty acid synthase; the HOXB13 G84E mutation disrupts this HOXB13-HDAC3 interaction, leading to lipid accumulation and increased cell motility and tumor metastasis. Co-immunoprecipitation for HOXB13-HDAC3 interaction, ChIP-seq, histone deacetylation assays, G84E mutant functional characterization, xenograft metastasis model, fatty acid synthase inhibitor rescue Nature genetics High 35468964
2014 The prostate cancer risk SNP rs339331 at 6q22 lies within a functional HOXB13-binding site; the risk T allele increases HOXB13 binding to a transcriptional enhancer, conferring allele-specific upregulation of RFX6 expression. ChIP-seq for HOXB13 binding, allele-specific reporter assays, HOXB13 knockdown with RFX6 expression readout Nature genetics High 24390282
2009 A FOXA1-binding 37-bp enhancer element downstream of the Hoxb13 coding region is required for prostate-specific transcriptional activation of Hoxb13; FOXA1 directly occupies this element in human prostate cancer cells. BAC-based reporter gene deletion analysis in transgenic mice, ChIP for FOXA1 binding, replacement of enhancer element with LoxP site Proceedings of the National Academy of Sciences of the United States of America High 20018680
2008 HDAC4 and YY1 form a complex that is recruited to HOXB13 promoter YY1-binding sites to repress HOXB13 expression via histone deacetylation in AR-negative prostate cancer cells; HDAC inhibitor NaB relieves this repression and induces cell growth arrest. Co-immunoprecipitation for HDAC4-YY1 complex, ChIP for HDAC4/YY1 at HOXB13 promoter, promoter truncation and point mutation reporter assays The international journal of biochemistry & cell biology Medium 19013255
2012 EZH2 recruits DNMT3b to the HOXB13 promoter to form a repression complex mediating DNA methylation and histone methylation; all-trans retinoic acid (ATRA) upregulates HOXB13 by decreasing EZH2 and DNMT3b expression and reducing their interaction with the HOXB13 promoter. ChIP for EZH2 and DNMT3b at HOXB13 promoter, Co-IP for EZH2-DNMT3b interaction, ATRA treatment with promoter methylation quantification PloS one Medium 22808286
2003 Loss-of-function mutations in Hoxb13 in mice cause overgrowth of the caudal spinal cord and tail vertebrae due to increased cell proliferation and decreased apoptosis in the tail bud; Hoxb13 functions as an inhibitor of neuronal cell proliferation and activator of apoptotic pathways in the secondary neural tube. Hoxb13 knockout mouse generation, beta-galactosidase reporter allele for expression mapping, histological analysis, cell proliferation and apoptosis quantification Developmental biology High 12679105
2003 Hoxb13 is required for normal differentiation and secretory function of the ventral prostate epithelium; loss of Hoxb13 leads to simple cuboidal rather than tall columnar epithelial cells and loss of ventral-specific secretory proteins (p12 and p25); Hoxb13/Hoxd13 double mutants show severe hypoplasia of duct tips, revealing redundancy in prostate morphogenesis. Hoxb13 loss-of-function mouse, Hoxb13/Hoxd13 double mutant, histological analysis, in situ hybridization for secretory protein expression Development (Cambridge, England) High 12668621
2005 HOXB13 suppresses growth of colorectal cancer cells by negatively regulating TCF-4 protein stability and its downstream targets c-myc and cyclin D1, inhibiting beta-catenin/TCF-mediated signaling; HOXB13 expression is lost or diminished in 62% of colorectal tumors. Forced expression of HOXB13 in CRC cells, TCF-4 reporter assay, western blot for TCF-4/c-myc/cyclin D1, in vitro and in vivo growth suppression assay British journal of cancer Medium 15928669
2006 HOXB13 is epigenetically silenced by CpG island methylation in renal cell carcinoma (RCC); exogenous HOXB13 expression in RCC cells lacking endogenous HOXB13 suppresses colony formation and induces apoptosis, supporting a tumor suppressor function. Methylated CpG island amplification/RDA, bisulfite restriction analysis, methyltransferase inhibitor reactivation, exogenous HOXB13 expression with colony formation and apoptosis assays Oncogene Medium 16278676
2010 DNMT3B directly targets the HOXB13 upstream CpG island for methylation in colon cancer; cells lacking both DNMT1 and DNMT3B show near-complete demethylation of this locus; HOXB13 expression suppresses colon cancer growth in vitro and abolishes tumor growth in nude mice. ChIP with DNMT3B antibody followed by CpG island microarray, MassARRAY methylation analysis, DNMT1/3B knockout cells, nude mouse xenograft tumor suppression assay PloS one Medium 20454457
2018 BRD4 epigenetically promotes HOXB13 expression in CRPC cells; pharmacological dual BET bromodomain-kinase inhibitors suppress HOXB13 mRNA and protein, directly correlating with apoptosis induction and inhibition of CRPC growth. BRD4 inhibition (pharmacological and genetic), HOXB13 mRNA/protein quantification, cell proliferation/apoptosis assays, integrative transcriptomic analysis Molecular cancer therapeutics Medium 30242092
2018 HBXIP prevents chaperone-mediated autophagy (CMA)-dependent degradation of HOXB13 by enhancing HOXB13 acetylation at lysine 277, causing HOXB13 accumulation; HBXIP also acts as a co-activator of HOXB13 to stimulate IL-6 transcription, promoting tamoxifen resistance in breast cancer. Co-IP, ChIP, luciferase reporter, western blot for acetylation at K277, site-directed mutagenesis of K277, cell viability and xenograft assays Journal of hematology & oncology Medium 29471853
2022 CBP/p300 mediates acetylation of HOXB13 at lysine 13 (K13); acK13-HOXB13 promotes expression of lineage genes (AR, HOXB13), CRPC-promoting genes (ACK1), and angiogenesis genes by establishing tumor-specific super enhancers; loss of K13 acetylation (HOXB13K13A mutant) reduces chromatin binding, self-renewal, and xenograft growth while increasing enzalutamide sensitivity. Mass spectrometry identification of K13 acetylation, ChIP-seq for super enhancers, HOXB13K13A isogenic mutants, organoid sensitivity assays, xenograft tumor models Clinical cancer research High 35849143
2020 MEIS1 tumor-suppressive activity in prostate cancer is dependent on HOXB13; MEIS1 and HOXB13 directly co-regulate proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression, as demonstrated by HOXB13 deletion abolishing MEIS1 anti-tumor effects. HOXB13 CRISPR deletion in context of MEIS1 expression, ChIP-seq plus RNA-seq integration, in vitro and in vivo xenograft models eLife High 32553107
2013 HOXB13 accumulates cells at G1 by promoting ubiquitination and degradation of cyclin D1, reducing pRb phosphorylation; depletion of HOXB13 increases cyclin B1 and CDC25C, activating CDK1 and facilitating G2/M transition. HOXB13 overexpression and siRNA knockdown in PC-3 and LNCaP cells, cell cycle analysis, western blot for cyclins/pRb/CDC25C, ubiquitination assay for cyclin D1 Molecular and cellular endocrinology Medium 24325868
2015 HOXB13 and ALX4 form a protein complex in ovarian cancer cells; either protein alone promotes EMT and invasion; both proteins transcriptionally upregulate SLUG expression, and SLUG is required for HOXB13- or ALX4-mediated EMT and invasion. Co-immunoprecipitation for HOXB13-ALX4 complex, knockdown/overexpression experiments, invasion assays, western blot for SLUG and EMT markers Oncotarget Medium 25944620
2020 FTO demethylates m6A modifications in the 3' UTR of HOXB13 mRNA, abolishing YTHDF2-mediated recognition and mRNA decay, thereby increasing HOXB13 protein expression, which activates WNT signaling and promotes endometrial cancer metastasis; WNT inhibitor ICG-001 blocks HOXB13-induced metastasis. MeRIP-seq for m6A sites, FTO overexpression/knockdown with HOXB13 mRNA stability assays, YTHDF2 interaction studies, in vivo metastasis model, ICG-001 rescue RNA biology Medium 33103587
2014 HOXB13 transcriptionally suppresses prostate-derived Ets factor (PDEF) expression, leading to upregulation of MMP-9 and survivin and promotion of prostate cancer cell invasion. DNA microarray, HOXB13 overexpression in PC3 cells, transwell invasion assay, gelatin zymography, western blot for MMP-9 and survivin International journal of oncology Medium 24898171
2019 HOXB13 directly binds to promoters of ABCG1, EZH2, and Slug to upregulate their expression, promoting lung adenocarcinoma metastasis and cisplatin resistance; cisplatin treatment further induces HOXB13 expression, creating a resistance loop. ChIP for HOXB13 binding at ABCG1/EZH2/Slug promoters, HOXB13 overexpression/knockdown with drug sensitivity assays, xenograft and patient-derived xenograft models Theranostics Medium 31037158
2018 HOXB13 binds to the CIP2A gene locus and functionally promotes CIP2A transcription in prostate cancer cells, with synergistic interaction between HOXB13 G84E and CIP2A R229Q variants conferring highest inherited prostate cancer risk. ChIP for HOXB13 at CIP2A locus, overexpression of variants with cell growth and migration readouts, genotyping cohort studies Clinical cancer research Medium 30181389
2005 Hoxb13 overexpression in an adult organotypic epidermal model decreases cell proliferation, increases apoptosis, and promotes excessive terminal differentiation characterized by enhanced transglutaminase activity and cornified envelope formation. Hoxb13 overexpression in organotypic epidermal model, transglutaminase activity assay, apoptosis and proliferation quantification, histological analysis The Journal of biological chemistry Medium 15964834
2019 HOXB13 regulates a mitotic protein-kinase interaction network; HOXB13 depletion increases HSPB8 mRNA expression in metastatic CRPC models, and increased HSPB8 expression suppresses CRPC cell migration; HOXB13 co-regulates mitotic kinases including AURKB and MELK. HOXB13 knockdown in CRPC cell lines, integrative bioinformatics of AR binding sites, HSPB8 overexpression migration assay, expression analysis in circulating tumor cells Scientific reports Low 31273254
2021 HOXB13 directly binds to and transcriptionally regulates the HOXA11-AS lncRNA promoter; the HOXB13/HOXA11-AS axis regulates CCL2/CCR2 signaling and integrin subunits (ITGAV, ITGB1) relevant to prostate cancer bone metastasis; HOXB13 co-regulates IBSP promoter in combination with HOXA11-AS. ChIP for HOXB13 at HOXA11-AS promoter, HOXB13 knockdown/overexpression with gene expression and invasion readouts, conditioned medium experiments with osteoblasts Genes Low 33514011
2003 HOXB13 protein is localized predominantly to the cytoplasm throughout fetal skin development, with only partial nuclear localization observed in adult epidermis; in Kaposi's sarcoma-associated epidermis, strong HOXB13 expression is partially nuclear, suggesting context-dependent compartmentalization. Immunofluorescence/immunohistochemistry on developing and adult skin tissue sections and Kaposi's sarcoma specimens Developmental dynamics Low 12761847
2020 HOXB13 promotes gastric cancer cell migration and invasion by transcriptionally upregulating IGF-1R, activating the PI3K/AKT/mTOR signaling pathway; FTO suppresses HOXB13 mRNA methylation, increasing HOXB13 protein and thus downstream IGF-1R/PI3K signaling. MeRIP-seq, luciferase reporter assay for HOXB13-IGF1R regulatory interaction, HOXB13/FTO knockdown with Transwell invasion/migration assays, western blot for PI3K/AKT/mTOR Life sciences Low 33894267
2022 HOXB13 activates PIMREG promoter transcription; elevated PIMREG in turn upregulates RAD51, BRCA1, and CDC25A/B/C while downregulating HIPK2, increasing DNA repair capacity and cell cycle progression to promote HCC drug resistance; HOXB13 acts through PIMREG rather than directly regulating these downstream targets. Luciferase reporter assay for PIMREG promoter, PIMREG knockdown in HOXB13-overexpressing cells, western blot for DNA repair/cell cycle proteins, in vivo xenograft model Biochemical and biophysical research communications Low 35878427

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Germline mutations in HOXB13 and prostate-cancer risk. The New England journal of medicine 530 22236224
2017 H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma. Nucleic acids research 274 27956498
2009 The homeodomain protein HOXB13 regulates the cellular response to androgens. Molecular cell 184 19917249
2014 A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding. Nature genetics 175 24390282
2013 Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. Journal of the National Cancer Institute 169 23812955
2018 CiRS-7 promotes growth and metastasis of esophageal squamous cell carcinoma via regulation of miR-7/HOXB13. Cell death & disease 166 30082829
2012 HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). Human genetics 153 23064873
2003 Hoxb13 is required for normal differentiation and secretory function of the ventral prostate. Development (Cambridge, England) 148 12668621
1996 Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains colinearity. Development (Cambridge, England) 143 8756292
2018 Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13. Proceedings of the National Academy of Sciences of the United States of America 131 29844167
2003 Hoxb13 mutations cause overgrowth of caudal spinal cord and tail vertebrae. Developmental biology 126 12679105
2004 HOXB13 induces growth suppression of prostate cancer cells as a repressor of hormone-activated androgen receptor signaling. Cancer research 125 15604291
2020 A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes. Nature 119 32499640
2012 A population-based assessment of germline HOXB13 G84E mutation and prostate cancer risk. European urology 111 22841674
2020 FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway. RNA biology 99 33103587
2007 HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 99 17308270
2007 HOXB13 promotes ovarian cancer progression. Proceedings of the National Academy of Sciences of the United States of America 99 17942676
2004 HOXB13 homeodomain protein suppresses the growth of prostate cancer cells by the negative regulation of T-cell factor 4. Cancer research 92 15126340
2022 HOXB13 suppresses de novo lipogenesis through HDAC3-mediated epigenetic reprogramming in prostate cancer. Nature genetics 87 35468964
2005 Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer. British journal of cancer 85 15583692
2013 HOXB13 mediates tamoxifen resistance and invasiveness in human breast cancer by suppressing ERα and inducing IL-6 expression. Cancer research 84 23832664
2015 Prevalence of the HOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes. Annals of oncology : official journal of the European Society for Medical Oncology 83 25595936
2001 Expression of Hoxb13 and Hoxc10 in developing and regenerating Axolotl limbs and tails. Developmental biology 80 11150241
2005 HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation. British journal of cancer 79 15928669
1998 Modulation of the human homeobox genes PRX-2 and HOXB13 in scarless fetal wounds. The Journal of investigative dermatology 75 9665387
2012 A novel germline mutation in HOXB13 is associated with prostate cancer risk in Chinese men. The Prostate 74 22718278
2013 HOXB13 G84E mutation in Finland: population-based analysis of prostate, breast, and colorectal cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 72 23292082
2006 Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene 72 16278676
2012 Confirmation of the HOXB13 G84E germline mutation in familial prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 71 22714738
2010 HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling. Molecular cancer 69 20504375
2016 Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer. Cancer letters 66 27018308
2018 Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer tamoxifen resistance in breast cancer. Journal of hematology & oncology 65 29471853
1999 Androgen-independent expression of hoxb-13 in the mouse prostate. The Prostate 64 10517879
2013 HOXB13 downregulates intracellular zinc and increases NF-κB signaling to promote prostate cancer metastasis. Oncogene 63 24096478
2018 MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease. Clinical cancer research : an official journal of the American Association for Cancer Research 62 29716922
2012 Association between germline HOXB13 G84E mutation and risk of prostate cancer. Journal of the National Cancer Institute 60 22781434
2010 HOXB13, a target of DNMT3B, is methylated at an upstream CpG island, and functions as a tumor suppressor in primary colorectal tumors. PloS one 59 20454457
2019 Circular RNA ITCH suppressed prostate cancer progression by increasing HOXB13 expression via spongy miR-17-5p. Cancer cell international 58 31827402
2019 HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients. Theranostics 56 31037158
2017 HOXB13 mutations and binding partners in prostate development and cancer: Function, clinical significance, and future directions. Genes & diseases 53 28798948
2007 Exploring the two-gene ratio in breast cancer--independent roles for HOXB13 and IL17BR in prediction of clinical outcome. Breast cancer research and treatment 49 17453342
2015 The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 46 26108461
2005 Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer. Oncology reports 45 15756448
2013 The G84E mutation of HOXB13 is associated with increased risk for prostate cancer: results from the REDUCE trial. Carcinogenesis 44 23393222
2022 A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry. European urology 43 35031163
2012 HOXB13 mutations in a population-based, case-control study of prostate cancer. The Prostate 43 23129385
2013 HOXB13 mutation and prostate cancer: studies of siblings and aggressive disease. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 39 23396964
2010 HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression. Anatomy & cell biology 39 21267402
2020 MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans. eLife 38 32553107
2015 HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells. Oncotarget 36 25944620
2017 Sensitivity of HOXB13 as a Diagnostic Immunohistochemical Marker of Prostatic Origin in Prostate Cancer Metastases: Comparison to PSA, Prostein, Androgen Receptor, ERG, NKX3.1, PSAP, and PSMA. International journal of molecular sciences 35 28555048
2015 Identification of Two Novel HOXB13 Germline Mutations in Portuguese Prostate Cancer Patients. PloS one 35 26176944
2021 HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway. Life sciences 34 33894267
2018 Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting with EZH2 in glioma. Cancer medicine 34 30105866
2015 Imputation of the rare HOXB13 G84E mutation and cancer risk in a large population-based cohort. PLoS genetics 34 25629170
2008 Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers. The international journal of biochemistry & cell biology 34 19013255
2015 HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy. Oncotarget 33 25825985
2014 HOXB13 G84E-related familial prostate cancers: a clinical, histologic, and molecular survey. The American journal of surgical pathology 33 24722062
2016 Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness. BJU international 32 26779768
2013 The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland. The Prostate 32 23334858
2013 G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 32 24026887
2011 Keratin 15, transcobalamin I and homeobox gene Hox-B13 expression in breast phyllodes tumors: novel markers in biological classification. Breast cancer research and treatment 32 21574054
2020 ACK1-AR and AR-HOXB13 signaling axes: epigenetic regulation of lethal prostate cancers. NAR cancer 31 32885168
2019 Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer. Signal transduction and targeted therapy 31 31815008
2013 HOXB13 is a sensitive and specific marker of prostate cells, useful in distinguishing between carcinomas of prostatic and urothelial origin. Virchows Archiv : an international journal of pathology 31 24146108
2013 HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease. Breast cancer research : BCR 30 23497539
2018 Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer. Molecular cancer therapeutics 29 30242092
2013 Population-based estimate of prostate cancer risk for carriers of the HOXB13 missense mutation G84E. PloS one 29 23457453
2012 ATRA inhibits the proliferation of DU145 prostate cancer cells through reducing the methylation level of HOXB13 gene. PloS one 29 22808286
2003 HOXB13 homeodomain protein is cytoplasmic throughout fetal skin development. Developmental dynamics : an official publication of the American Association of Anatomists 29 12761847
2019 The Homeobox gene, HOXB13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers. Scientific reports 28 31273254
2023 Characterization of HOXB13 expression patterns in localized and metastatic castration-resistant prostate cancer. The Journal of pathology 27 37850574
2019 HOXB13 promotes proliferation, migration, and invasion of glioblastoma through transcriptional upregulation of lncRNA HOXC-AS3. Journal of cellular biochemistry 27 31062400
2021 Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression. Scientific reports 26 33531604
2017 Computational Modeling of complete HOXB13 protein for predicting the functional effect of SNPs and the associated role in hereditary prostate cancer. Scientific reports 26 28272408
2013 Germline HOXB13 p.Gly84Glu mutation and risk of colorectal cancer. Cancer epidemiology 26 23541221
2018 HOXB13 expression and promoter methylation as a candidate biomarker in gastric cancer. Oncology letters 25 29928325
2020 Somatic HOXB13 Expression Correlates with Metastatic Progression in Men with Localized Prostate Cancer Following Radical Prostatectomy. European urology oncology 24 32540218
2020 Mutation HOXB13 c.853delT in Martinican prostate cancer patients. The Prostate 23 32040869
2009 A FOXA1-binding enhancer regulates Hoxb13 expression in the prostate gland. Proceedings of the National Academy of Sciences of the United States of America 23 20018680
2021 Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes in Prostate Cancer. Genes 22 33514011
2015 Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression. Asian Pacific journal of cancer prevention : APJCP 22 25743797
2014 Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer. Pharmacogenomics and personalized medicine 22 25206306
2013 HOXB13 contributes to G1/S and G2/M checkpoint controls in prostate. Molecular and cellular endocrinology 22 24325868
2005 Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation in an epidermal organotypic model. The Journal of biological chemistry 22 15964834
2022 Acetylated HOXB13 Regulated Super Enhancer Genes Define Therapeutic Vulnerabilities of Castration-Resistant Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 21 35849143
2020 MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity. Oncogene 21 32681068
2015 HOXB13 as an immunohistochemical marker of prostatic origin in metastatic tumors. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 21 26590121
2018 Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 20 30181389
2014 Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy. BJU international 20 24148311
2020 LncRNA SNHG14 regulates the DDP-resistance of non-small cell lung cancer cell through miR-133a/HOXB13 pathway. BMC pulmonary medicine 19 33059643
2020 Germline HOXB13 G84E mutation carriers and risk to twenty common types of cancer: results from the UK Biobank. British journal of cancer 18 32830201
2014 HOXB13 regulates the prostate-derived Ets factor: implications for prostate cancer cell invasion. International journal of oncology 18 24898171
2020 Pathogenic Germline DNA Repair Gene and HOXB13 Mutations in Men With Metastatic Prostate Cancer. JCO precision oncology 17 32923906
2017 HOXB13 a useful marker in pleomorphic giant cell adenocarcinoma of the prostate: a case report and review of the literature. Virchows Archiv : an international journal of pathology 17 28484843
2015 Germline HOXB13 p.Gly84Glu mutation and cancer susceptibility: a pooled analysis of 25 epidemiological studies with 145,257 participates. Oncotarget 17 26517352
2012 Evaluation of HOXB13 as a molecular marker of recurrent prostate cancer. Molecular medicine reports 17 22293681
2022 HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway. Journal of Zhejiang University. Science. B 15 35557042
2022 Excessive activation of HOXB13/PIMREG axis promotes hepatocellular carcinoma progression and drug resistance. Biochemical and biophysical research communications 15 35878427
2016 Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis. Oncotarget 15 27626483

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