Affinage

HOXB9

Homeobox protein Hox-B9 · UniProt P17482

Length
250 aa
Mass
28.1 kDa
Annotated
2026-06-10
61 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXB9 is a homeodomain transcription factor that specifies positional and skeletal identity during development and is repeatedly co-opted as a driver of cancer invasion and metastasis (PMID:9013929, PMID:19576624, PMID:20080567). In the embryo it acts together with paralogous Hox9 genes: loss of Hoxb9 disrupts rib and sternum morphogenesis with synergistic defects in Hoxa9 double mutants (PMID:9013929), and Hoxa9/Hoxb9/Hoxd9 triple mutants fail in pregnancy-induced mammary ductal expansion (PMID:9892669), consistent with HOXB9's intrinsic capacity to specify intermediate antero-posterior identity when expressed heterologously (PMID:8105876). Its transcriptional output depends on the homeodomain for promoter occupancy (PMID:22863320) and is enhanced by the BTG1/BTG2 co-factors, which bind HOXB9 and stabilize its DNA binding through its N-terminal activation domain (PMID:10617598); in gastric cancer HOXB9 partners with PBX2 to form a heterodimer that activates CDK6 and drives G1-to-S progression (PMID:37272544). Across multiple tumor types HOXB9 directly binds and activates target promoters to promote proliferation, EMT, angiogenesis, and metastasis, including JMJD6 (PMID:27613418), E2F3 (PMID:29724991), miR-765 (PMID:29408459), MMP12 (PMID:38632141), SLC7A11 (PMID:39127016), SDC4 (PMID:40571266), and IL15RA (PMID:42168464), and induces angiogenic and ErbB-ligand programs (PMID:20080567); conversely it can act as a tumor suppressor by binding the RBL2 promoter to enforce G0/G1 arrest (PMID:35182659). HOXB9 abundance, localization, and activity are tightly controlled by post-translational modification: PCAF acetylates HOXB9 at K27 (reversed by SIRT1), driving nuclear-to-cytoplasmic relocation that suppresses oncogenic targets such as JMJD6 and EZH2 (PMID:27613418, PMID:29654889), while AMPKα phosphorylation at T133 licenses Praja2-mediated ubiquitination and proteasomal degradation that limits KRAS induction (PMID:36001969), and TRIM11 ubiquitinates HOXB9 to reverse its NF-κB-activating activity (PMID:39903348). HOXB9 transcription is itself a convergence point for WNT/β-catenin/TCF (PMID:19576624, PMID:26544896), E2F1 (PMID:25136922), estrogen-receptor/MLL signaling (PMID:21428455), and an ERK5–BMI1 axis (PMID:17148583), and its mRNA is stabilized by IGF2BP3 in an m6A-dependent manner (PMID:42168464).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 Medium

    Established that mammalian HOXB9 is a bona fide positional-identity selector by showing it can impose homeotic transformations in a heterologous organism.

    Evidence Heat-shock-driven mouse HoxB9 expression in transgenic Drosophila scoring homeotic transformations

    PMID:8105876

    Open questions at the time
    • Heterologous system does not define endogenous mammalian targets
    • No molecular partners or DNA targets identified
  2. 1997 High

    Defined HOXB9's endogenous developmental role and its functional cooperativity with a paralog by genetic loss-of-function.

    Evidence Targeted disruption of hoxb-9 in mice with hoxa-9 double-mutant epistasis analysis of rib/sternum phenotypes

    PMID:9013929

    Open questions at the time
    • Molecular basis of paralog synergy not resolved
    • Direct target genes in skeletal patterning unknown
  3. 1999 High

    Extended HOXB9 function beyond skeletal patterning to organ morphogenesis, showing redundancy across Hox9 paralogs in mammary development.

    Evidence Hoxa9/Hoxb9/Hoxd9 triple-mutant mice with histological mammary gland analysis

    PMID:9892669

    Open questions at the time
    • Does not separate HOXB9-specific from shared paralog contributions
    • Downstream effectors in ductal expansion not identified
  4. 2000 High

    Provided the first direct biochemical mechanism for HOXB9 transactivation by identifying co-factors that enhance its DNA binding.

    Evidence Yeast two-hybrid, co-IP, EMSA, and reporter assays defining BTG1/BTG2 interaction and N-terminal activation domain dependence

    PMID:10617598

    Open questions at the time
    • Physiological target genes co-regulated by BTG proteins not defined
    • Structural basis of binding enhancement unknown
  5. 2007 Medium

    Placed HOXB9 transcription within an upstream signaling hierarchy in lymphoma and linked it to proliferation/apoptosis.

    Evidence Expression profiling and knockdown/overexpression mapping an ERK5–BMI1–E2F3A axis controlling HOXB9 in Hodgkin lymphoma cells

    PMID:17148583

    Open questions at the time
    • No direct binding of E2F3A/BMI1 to HOXB9 promoter shown
    • HOXB9 effector targets in this context not identified
  6. 2009 High

    Identified HOXB9 as a metastasis-driving WNT/TCF effector and characterized its angiogenic/EMT transcriptional program.

    Evidence WNT/TCF target identification with shRNA knockdown and in vivo brain/bone metastasis assays; overexpression with xenograft metastasis and target-gene profiling

    PMID:19576624 PMID:20080567

    Open questions at the time
    • Direct promoter occupancy on individual angiogenic targets not established here
    • Mechanism distinguishing primary growth from metastasis incomplete
  7. 2012 Medium

    Demonstrated the homeodomain is required for HOXB9 promoter occupancy and oncogenic transformation activity.

    Evidence ChIP, reporter assays, homeodomain mutagenesis, and soft-agar colony formation

    PMID:22863320

    Open questions at the time
    • Single lab
    • Co-factor requirements for site selection not defined
  8. 2011 Medium

    Defined hormone-responsive transcriptional control of HOXB9 by estrogen receptors and chromatin-modifying co-regulators.

    Evidence Reporter assays, ChIP, and siRNA showing ERα/ERβ and MLL1/MLL3 binding to HOXB9 promoter EREs (extended to BPA/CBP-P300 in 2016)

    PMID:21428455 PMID:27182052

    Open questions at the time
    • Single lab
    • In vivo physiological relevance of ER-driven HOXB9 in normal tissue limited
  9. 2014 Medium

    Identified E2F1 and CDK4/6 signaling as direct upstream activators of HOXB9 transcription in breast cancer.

    Evidence EMSA, ChIP, promoter mutation, and dual-luciferase mapping E2F1 binding at –404/–392

    PMID:25136922

    Open questions at the time
    • Single lab
    • Generalizability beyond breast cancer untested
  10. 2016 High

    Established acetylation as a master switch governing HOXB9 oncogenic versus suppressive output by defining its writer, eraser, and site.

    Evidence In vitro/in vivo acetylation assays, K27 mutagenesis, PCAF/SIRT1 identification, ChIP on JMJD6, and xenograft (extended in 2018 to nuclear-cytoplasmic relocation and EZH2)

    PMID:27613418 PMID:29654889

    Open questions at the time
    • Nuclear export machinery responding to AcK27 not identified
    • Determinants selecting which targets are switched off unclear
  11. 2015 Medium

    Mapped multiple upstream pathways and an intramolecular brake controlling HOXB9 activity across cancer types.

    Evidence Pathway epistasis for GalNAc-T14/WNT/β-catenin and TGFβ1/Kindlin-2 axes; hexapeptide-deletion mutagenesis defining a negative regulatory motif in gastric cancer

    PMID:25081022 PMID:25724625 PMID:26536658 PMID:26544896

    Open questions at the time
    • Context-dependence of oncogenic vs suppressive HOXB9 not mechanistically unified
    • Some links rely on single-method functional assays
  12. 2018 Medium

    Expanded the direct HOXB9 target repertoire to non-coding and proliferative effectors driving stemness and migration.

    Evidence ChIP and luciferase validating direct binding to miR-765 and E2F3 promoters with knockdown/rescue and xenografts

    PMID:29408459 PMID:29724991

    Open questions at the time
    • Single lab per target
    • Cross-tumor conservation of these targets untested
  13. 2022 High

    Revealed a phosphodegron controlling HOXB9 stability and identified its kinase and E3 ligase, linking metabolic signaling to HOXB9-driven KRAS expression.

    Evidence In vitro kinase assay, T133A mutagenesis, co-IP, AMPKα/Praja2 identification, KRAS target validation, and xenograft (RBL2 cell-cycle target defined same year)

    PMID:35182659 PMID:36001969

    Open questions at the time
    • Stoichiometry of AMPK–Praja2 coupling unresolved
    • How phosphorylation/acetylation switches are integrated unknown
  14. 2023 High

    Identified PBX2 as a direct heterodimerization partner that channels HOXB9 to a CDK6-driven proliferation program.

    Evidence Reciprocal co-IP, ChIP, luciferase on CDK6, knockdown with CDK6 epistasis rescue, and xenograft in gastric cancer

    PMID:37272544

    Open questions at the time
    • Whether PBX2 partnership generalizes to other HOXB9 targets unknown
    • Structural basis of the heterodimer not resolved
  15. 2024 Medium

    Connected HOXB9 to redox/ferroptosis and barrier-disruption programs and refined PTM control of its stability.

    Evidence ChIP/luciferase on SLC7A11, MMP12, SPP1, and SDC4 promoters; CAP-induced PCAF-HOXB9 acetylation and ubiquitination assays; in vivo barrier and xenograft models

    PMID:38621423 PMID:38632141 PMID:39127016 PMID:40571266

    Open questions at the time
    • Single lab per target
    • Interplay between acetylation and ubiquitination on stability not fully resolved
  16. 2026 Medium

    Added post-transcriptional m6A control of HOXB9 abundance feeding an IL-15 signaling axis in metastasis.

    Evidence RIP, m6A assays, and metastasis models showing IGF2BP3 stabilizes HOXB9 mRNA driving IL15RA transcription

    PMID:42168464

    Open questions at the time
    • Single lab
    • Relative contribution of mRNA vs protein-level control to HOXB9 levels unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HOXB9 selects between oncogenic and tumor-suppressive transcriptional programs across tissues, and how its competing acetylation, phosphorylation, ubiquitination, and m6A controls are integrated in vivo, remains unresolved.
  • No unified model linking PTM state to target-gene selection
  • Structural basis of HOXB9 cofactor (BTG, PBX2) complexes undefined
  • Genome-wide direct binding landscape not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2
Partners
BTG1BTG2IGF2BP3PBX2PCAFPRAJA2SIRT1TRIM11

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 BTG1 and BTG2 physically interact with HOXB9 (identified by yeast two-hybrid screening) and enhance HOXB9-mediated transcription in transfected cells. A HOXB9·BTG2 complex forms on a HOXB9-responsive target, and this interaction facilitates HOXB9 binding to DNA. The transcriptional activation is dependent on the N-terminal activation domain of HOXB9. Yeast two-hybrid screening, co-immunoprecipitation, transcription reporter assay, EMSA/DNA-binding assay The Journal of biological chemistry High 10617598
1997 Targeted disruption of hoxb-9 in mice causes defects in first and second rib development and sternum morphogenesis; double mutants with hoxa-9 show synergistic (more severe) rib and sternal phenotypes, establishing that HOXB9 and HOXA9 function together in specification of thoracic skeletal elements. Targeted gene disruption in mice, genetic epistasis/double-mutant analysis Developmental biology High 9013929
1999 Paralogous Hox genes Hoxa9, Hoxb9, and Hoxd9 are required for expansion and/or differentiation of mammary epithelial ductal system in response to pregnancy, demonstrated by triple mutant mice that cannot raise pups due to impaired mammary gland development. Targeted gene disruption in mice (triple mutant), histological analysis of mammary gland Proceedings of the National Academy of Sciences of the United States of America High 9892669
1993 Mouse HoxB9 expressed from a heat-shock promoter in Drosophila induces anterior-to-posterior homeotic transformations in larvae and adults, demonstrating functional similarity to Drosophila Abdominal-B and intermediate positional identity specification between Antennapedia and Abdominal-B. Transgenic Drosophila heat-shock expression, phenotypic analysis of homeotic transformations Mechanisms of development Medium 8105876
2009 HOXB9 is a WNT/TCF target gene that mediates chemotactic invasion and colony outgrowth in lung adenocarcinoma cells; reduction of TCF activity attenuates brain and bone metastasis independently of effects on primary lung tumor growth, placing HOXB9 downstream of hyperactive WNT/TCF signaling in the metastatic program. Gene expression profiling, shRNA knockdown, in vivo metastasis assays (brain/bone colonization in mice) Cell High 19576624
2009 HOXB9 as a transcription factor induces expression of angiogenic factors (VEGF, bFGF, IL-8, ANGPTL-2), ErbB ligands (amphiregulin, epiregulin, neuregulins), and TGF-β, leading to increased cell motility, EMT acquisition, and in vivo tumor growth with lung metastasis in breast cancer. Overexpression in breast cancer cell lines, in vivo xenograft/metastasis assay, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 20080567
2016 PCAF acetyltransferase interacts with and acetylates HOXB9 at lysine 27 (K27) both in vivo and in vitro; this acetylation is reversed by SIRT1 deacetylase. AcK27-HOXB9 suppresses transcription of its target gene JMJD6 by occupying the JMJD6 promoter, decreasing lung cancer cell migration and tumor growth compared to non-acetylated HOXB9. Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis (K27), ChIP assay, luciferase reporter assay, xenograft mouse model Nucleic acids research High 27613418
2018 Acetylation of HOXB9 at K27 causes its translocation from the nucleus to the cytoplasm, switching its function: non-acetylated HOXB9 promotes EZH2 expression and colon cancer progression, while AcK27-HOXB9 suppresses EZH2 transcription by relocating out of the nucleus. Subcellular fractionation, immunofluorescence, luciferase reporter assay, Western blot, immunohistochemistry Cancer letters Medium 29654889
2011 HOXB9 gene transcription is activated by estrogen (E2) through estrogen receptors ERα and ERβ binding to estrogen-response elements (EREs) in the HOXB9 promoter; histone methylases MLL1 and MLL3 also bind to HOXB9 EREs and are required for E2-mediated transcriptional activation. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), siRNA knockdown Biochemistry Medium 21428455
2016 Bisphenol-A (BPA) induces HOXB9 expression via EREs in the HOXB9 promoter, requiring estrogen receptors and co-regulators MLL3 histone methylase, CBP/P300 histone acetylases; these factors are recruited to HOXB9 promoter EREs in the presence of BPA, leading to chromatin modification (histone methylation and acetylation) and gene activation. Luciferase reporter assay, ChIP assay, in vivo animal experiment (ovariectomized rats), cell-based expression assays Gene Medium 27182052
2007 In Hodgkin lymphoma cells, HOXB9 expression is regulated by E2F3A (activator) and BMI1 (repressor); a constitutively active ERK5 pathway represses BMI1, thereby increasing HOXB9 expression. HOXB9 knockdown and overexpression influence both proliferation and apoptosis in HL cells. RT-PCR, microarray profiling, knockdown/overexpression functional assays Blood Medium 17148583
2008 The Hoxb9 promoter forms secondary DNA structures that regulate promoter activity; FBXL10 was identified as a protein that specifically binds the secondary-structured promoter DNA and affects Hoxb9 promoter activity. Promoter activity assays in cultured cells, nuclear extract binding assays, candidate gene isolation Nucleic acids research Medium 18276649
2012 HOXB9 binds to the promoters of tumor growth and angiogenic factors and regulates their expression; the HOXB9 homeodomain is required for this transcriptional regulatory activity and for 3D colony formation in soft agar. ChIP assay (promoter binding), reporter assays, homeodomain deletion/mutation analysis, soft agar colony formation assay The FEBS journal Medium 22863320
2014 E2F1 directly binds the HOXB9 promoter region (–404 to –392) and transcriptionally activates HOXB9 in breast cancer cells; CDK4/6 inhibition reduces E2F1 and consequently reduces HOXB9 and its downstream target genes. Dual luciferase reporter assay, EMSA, ChIP, mutation analysis of the TFBS, Q-PCR PloS one Medium 25136922
2015 HOXB9 promotes invasion and metastasis in pancreatic ductal adenocarcinoma through downregulation of E-cadherin; Kindlin-2, itself upregulated by TGF-β1, promotes PDAC progression by downregulating HOXB9 and E-cadherin, placing HOXB9 downstream of a TGF-β1/Kindlin-2 axis. Knockdown/overexpression in PDAC cells, Western blot, migration/invasion assays, in vivo xenograft Cancer letters Medium 25724625
2014 HOXB9 promotes EMT in hepatocellular carcinoma cells; knockdown of HOXB9 decreased migration and invasion, while overexpression increased them. TGF-β1 pathway activation is required for HOXB9-induced EMT in HCC cells. shRNA knockdown, overexpression, migration/invasion assays, Western blot for EMT markers Clinical and experimental medicine Low 25081022
2018 HOXB9 directly binds the promoter of microRNA-765 and facilitates its transcription; miR-765 in turn targets FOXA2, reducing FOXA2 levels and promoting cancer stem cell self-renewal and ER stress resistance in melanoma. ChIP assay, luciferase reporter assay, overexpression/knockdown, xenograft mouse model The Journal of investigative dermatology Medium 29408459
2018 HOXB9 promotes E2F3 expression by directly targeting its promoter in endometrial cancer cells; knockdown of E2F3 abolishes HOXB9-enhanced cell migration, placing E2F3 downstream of HOXB9 in this cancer context. ChIP assay, luciferase reporter assay, siRNA knockdown, migration assay Cell death & disease Medium 29724991
2022 AMPKα phosphorylates HOXB9 at threonine 133 (T133), promoting E3 ligase Praja2-mediated ubiquitination and proteasomal degradation of HOXB9 in lung adenocarcinoma cells. Blocking T133 phosphorylation (HOXB9 T133A mutant or AMPKα1/2 depletion) stabilizes HOXB9 and upregulates its target gene KRAS, promoting tumor growth. In vitro kinase assay, site-directed mutagenesis (T133A), co-immunoprecipitation, xenograft mouse model, LUAD patient sample analysis Cell reports High 36001969
2022 HOXB9 directly regulates cell cycle progression in pancreatic cancer by binding the RBL2 promoter to upregulate RBL2 and inhibiting c-Myc, causing G0/G1 arrest; DNMT1 suppresses HOXB9 expression by promoting methylation of its promoter. ChIP-qPCR, luciferase reporter assay, flow cytometry (cell cycle), cell cycle PCR array, xenograft and PDX mouse models Cancer letters Medium 35182659
2015 GalNAc-T14 increases β-catenin protein stability, leading to activated WNT signaling that induces HOXB9 expression; pharmacological inhibition of β-catenin suppresses HOXB9 expression and invasion, placing HOXB9 downstream of GalNAc-T14/WNT/β-catenin in lung cancer metastasis. Microarray, Western blot, pharmacological inhibition of β-catenin, invasion assays Oncotarget Medium 26544896
2019 GRP78 chaperones LRP6, promoting its maturation; knockdown of GRP78 leads to LRP6 misfolding and ERAD-dependent degradation, reducing mature LRP6 levels and thereby suppressing Wnt/HOXB9 signaling and HCC invasion/metastasis. HOXB9 overexpression rescues invasion/metastasis upon GRP78 knockdown. Knockdown (GRP78), overexpression (HOXB9), Western blot, co-immunoprecipitation, invasion/metastasis assays Experimental cell research Medium 31310747
2015 The hexapeptide motif of HOXB9 acts as a negative regulatory element ('brake') on its MET-inducing and tumor-suppressive activity in gastric carcinoma; a HOXB9 mutant lacking the hexapeptide motif shows more potent MET induction and tumor suppression than wild-type HOXB9. Site-directed mutagenesis (hexapeptide motif deletion), overexpression in gastric cancer cell lines, migration/invasion assays, in vivo xenograft Oncotarget Medium 26536658
2020 HOXB9-dependent expression of MMP9 in NSCLC cells leads to reduced expression of junctional proteins in vascular endothelial cells and enhanced transmigration of tumor cells through an in vitro blood-brain barrier model, establishing a mechanism for HOXB9-driven brain metastasis. In vitro BBB model (endothelial monolayer), shRNA knockdown and overexpression of HOXB9, measurement of junctional proteins, transmigration assay, in vivo brain metastasis in mice Aging Medium 33411683
2023 HOXB9 interacts with PBX2 to form a heterodimer that transcriptionally upregulates CDK6, promoting G1-to-S phase cell cycle progression and gastric cancer cell division; HOXB9 depletion causes G1 arrest that is phenocopied by CDK6 knockdown, and CDK6 knockdown reverses HOXB9-driven tumor growth. Co-immunoprecipitation (HOXB9-PBX2), ChIP, luciferase reporter assay, shRNA knockdown, cell cycle analysis, xenograft mouse model The Journal of pathology High 37272544
2016 HOXB9 expression is triggered by amino acid deprivation via activating transcription factor 4 (ATF4) in activated T cells; HOXB9 in turn suppresses NF-κB, NFAT, and AP-1 activities, attenuating selective cytokine production in response to amino acid starvation. siRNA knockdown, overexpression, reporter assays for NF-κB/NFAT/AP-1, amino acid deprivation experiments Immunology and cell biology Low 26926958
2024 HOXB9 directly binds to the promoter of SLC7A11 and transcriptionally upregulates its expression; cold atmospheric plasma (CAP) promotes HOXB9 interaction with PCAF, enhancing HOXB9 acetylation, which affects its ubiquitination and protein stability, ultimately downregulating HOXB9/SLC7A11 and promoting ferroptosis in lung cancer cells. Luciferase assay, ChIP, co-immunoprecipitation (HOXB9-PCAF), ubiquitination assay, overexpression/knockdown, in vivo xenograft Redox biology Medium 39127016
2025 TRIM11 acts as an E3 ubiquitin ligase that ubiquitinates HOXB9, promoting its degradation and reversing HOXB9-induced NF-κB pathway activation; simultaneous downregulation of TRIM11 and HOXB9 balances inflammation and apoptosis responses in LPS-stimulated THP-1 cells. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, Western blot, flow cytometry, ELISA Molecular biology reports Medium 39903348
2016 Dynamic subcellular localization of HOXB9 protein was characterized during mammalian early embryonic development by immunofluorescence: HOXB9 is mainly nuclear from immature oocyte to blastocyst stage in both mouse and bovine, with trophoblastic cells showing strong nuclear staining while inner cell mass/epiblast cells show dynamic variation in localization including cytoplasmic pools, and HOXB9 is detected in apical vacuoles of mouse visceral endoderm cells. Immunofluorescence microscopy across developmental stages (mouse and bovine), subcellular localization analysis PloS one Medium 27798681
2025 HOXB9 directly binds the SDC4 promoter (site 2) and activates SDC4 transcription, as confirmed by ChIP and dual-luciferase reporter assay. HOXB9 overexpression promotes SDC4 expression and PKCα activation, leading to reduced tight junction proteins and BBB disruption under ischemic conditions. ChIP assay, dual-luciferase reporter assay, overexpression, TEER assay, immunofluorescence, in vivo MCAO rat model Brain research bulletin Medium 40571266
2024 HOXB9 directly binds the promoter of MMP12 and transcriptionally activates it in laryngeal squamous cell carcinoma; CRISPR/Cas9 knockout of HOXB9 suppresses cell proliferation, migration, invasion and reduces MMP12 expression. CRISPR/Cas9 knockout, ChIP, dual-luciferase reporter assay, microarray, Western blot, immunohistochemistry, in vivo xenograft Functional & integrative genomics Medium 38632141
2024 HOXB9 directly binds the SPP1 promoter and transcriptionally upregulates SPP1 expression, protecting osteosarcoma cells from death under glucose starvation conditions. ChIP assay, luciferase reporter assay, overexpression/knockdown, cell viability assay under glucose deprivation Biochemical pharmacology Low 38621423
2026 IGF2BP3 binds and stabilizes HOXB9 mRNA in an m6A-dependent manner, increasing HOXB9 protein levels; HOXB9 then transcriptionally activates IL15RA expression, and IL-15/IL15RA signaling promotes migration, invasion, and in vivo metastasis of TNBC cells. RNA immunoprecipitation (RIP), Western blot, m6A assay, overexpression/knockdown, in vivo metastasis model Functional & integrative genomics Medium 42168464

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell 506 19576624
1999 Paralogous mouse Hox genes, Hoxa9, Hoxb9, and Hoxd9, function together to control development of the mammary gland in response to pregnancy. Proceedings of the National Academy of Sciences of the United States of America 156 9892669
2009 HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proceedings of the National Academy of Sciences of the United States of America 140 20080567
2000 The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation. The Journal of biological chemistry 123 10617598
2016 A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nature communications 104 27041221
1997 Targeted mutations in hoxa-9 and hoxb-9 reveal synergistic interactions. Developmental biology 101 9013929
2017 MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9. Oncogenesis 81 29199273
2016 PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6. Nucleic acids research 67 27613418
2000 A large targeted deletion of Hoxb1-Hoxb9 produces a series of single-segment anterior homeotic transformations. Developmental biology 58 10885747
2018 HOXB9 promotes endometrial cancer progression by targeting E2F3. Cell death & disease 57 29724991
2007 Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1. Blood 57 17148583
2015 Kindlin-2 induced by TGF-β signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9. Cancer letters 54 25724625
2015 The role of HOXB9 and miR-196a in head and neck squamous cell carcinoma. PloS one 54 25860510
2012 Homeodomain-containing protein HOXB9 regulates expression of growth and angiogenic factors, facilitates tumor growth in vitro and is overexpressed in breast cancer tissue. The FEBS journal 51 22863320
2016 Endocrine disrupting chemical, bisphenol-A, induces breast cancer associated gene HOXB9 expression in vitro and in vivo. Gene 48 27182052
2012 HOXB9 expression promoting tumor cell proliferation and angiogenesis is associated with clinical outcomes in breast cancer patients. Annals of surgical oncology 47 22396001
2022 HOXB9 blocks cell cycle progression to inhibit pancreatic cancer cell proliferation through the DNMT1/RBL2/c-Myc axis. Cancer letters 40 35182659
2018 Regulation of Cancer Stem Cell Self-Renewal by HOXB9 Antagonizes Endoplasmic Reticulum Stress-Induced Melanoma Cell Apoptosis via the miR-765-FOXA2 Axis. The Journal of investigative dermatology 39 29408459
2014 HOXB9 promotes epithelial-to-mesenchymal transition via transforming growth factor-β1 pathway in hepatocellular carcinoma cells. Clinical and experimental medicine 35 25081022
2014 Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients. British journal of cancer 34 25025961
2019 GRP78 activates the Wnt/HOXB9 pathway to promote invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6. Experimental cell research 32 31310747
2015 GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma. Oncotarget 29 26544896
2009 Do HOXB9 and COL1A1 genes play a role in congenital dislocation of the hip? Study in a Caucasian population. Osteoarthritis and cartilage 29 19341834
2011 Histone methylases MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression. Biochemistry 28 21428455
1993 Functional analysis of the mouse homeobox gene HoxB9 in Drosophila development. Mechanisms of development 27 8105876
2015 HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif. Oncotarget 26 26536658
2018 HOXB9 acetylation at K27 is responsible for its suppression of colon cancer progression. Cancer letters 22 29654889
2018 HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 22 30314948
2024 Cold atmospheric plasma enhances SLC7A11-mediated ferroptosis in non-small cell lung cancer by regulating PCAF mediated HOXB9 acetylation. Redox biology 21 39127016
2017 HoxB9 promotes the migration and invasion via TGF-β1/Smad2/Slug signaling pathway in oral squamous cell carcinoma. American journal of translational research 21 28386341
2021 Genome-Wide Epigenetic Landscape of Lung Adenocarcinoma Links HOXB9 DNA Methylation to Intrinsic EGFR-TKI Resistance and Heterogeneous Responses. JCO precision oncology 20 34036228
2014 An E2F1-HOXB9 transcriptional circuit is associated with breast cancer progression. PloS one 18 25136922
2022 HOXB9 Overexpression Promotes Colorectal Cancer Progression and Is Associated with Worse Survival in Liver Resection Patients for Colorectal Liver Metastases. International journal of molecular sciences 17 35216396
2023 The E2F1-HOXB9/PBX2-CDK6 axis drives gastric tumorigenesis and serves as a therapeutic target in gastric cancer. The Journal of pathology 14 37272544
2020 HOXB9 enhances the ability of lung cancer cells to penetrate the blood-brain barrier. Aging 14 33411683
2019 Experimental and clinicopathological analysis of HOXB9 in gastric cancer. Oncology letters 14 30867739
2003 [Transmission disequilibrium test for congenital dislocation of the hip and HOXB9 gene or COL1AI gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 14 12778441
2022 The AMPK-HOXB9-KRAS axis regulates lung adenocarcinoma growth in response to cellular energy alterations. Cell reports 13 36001969
2021 A Systematic Review on HOX Genes as Potential Biomarkers in Colorectal Cancer: An Emerging Role of HOXB9. International journal of molecular sciences 13 34948228
2016 Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals. PloS one 13 27798681
2021 miR-557 suppressed the malignant behaviours of osteosarcoma cells by reducing HOXB9 and deactivating the EMT process. Artificial cells, nanomedicine, and biotechnology 12 33666541
2008 Secondary DNA structure formation for Hoxb9 promoter and identification of its specific binding protein. Nucleic acids research 12 18276649
2022 HOXB9 mediates resistance to chemotherapy and patient outcomes through the TGFβ pathway in pancreatic cancer. Oncotarget 10 35634239
2016 HOXB9 acts as a negative regulator of activated human T cells in response to amino acid deficiency. Immunology and cell biology 10 26926958
2023 HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP. International journal of molecular sciences 9 36674764
2023 HOXB9 a miR-122-5p regulated gene, suppressed the anticancer effects of brusatol by upregulating SCD1 expression in melanoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 9 37031492
2019 Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma. Frontiers of medicine 7 31372881
2024 HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression. Biochemical pharmacology 6 38621423
2022 Activation of CTHRC1 by HOXB9 Promotes Angiogenesis through Fatty Acid Metabolism in Lung Adenocarcinoma. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 6 37205792
2020 Silencing of HOXB9 suppresses cellular proliferation, angiogenesis, migration and invasion of prostate cancer cells. Journal of biosciences 6 32098919
2025 The miR-192/EGR1-HOXB9 loop inhibits immune evasion in glioma by arresting their NSC phenotypes. International immunopharmacology 4 40090079
2024 HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12. Functional & integrative genomics 4 38632141
2016 Immunoexpression of hoxb7 and hoxb9 in salivary gland tumours. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 4 26991799
2025 Endothelial HOXB9/SDC4 signaling exacerbates post-ischemic blood-brain and blood-spinal cord barrier disruption by promoting PKCα activation. Brain research bulletin 2 40571266
2020 Identification of a Modified HOXB9 mRNA in Breast Cancer. Journal of oncology 2 32104178
2025 The miR-192-EGR1/HOXB9 Loop Regulates Glioma Cell Stemness and Malignant Phenotypes by Promoting Their Mesenchymal Transition. Journal of cellular and molecular medicine 1 40936205
2024 HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis. Journal of applied genetics 1 38753266
2026 The m6A reader IGF2BP3 promotes triple-negative breast cancer metastasis through HOXB9-IL15RA pathway. Functional & integrative genomics 0 42168464
2025 TRIM11 modulates sepsis progression by promoting HOXB9 ubiquitination and inducing the NF-κB signaling pathway. Molecular biology reports 0 39903348
2025 The roles of HOXB9 and MMP12 in proliferation, migration, and invasion of human laryngeal cancer cells LCC and TU212. Biochemical and biophysical research communications 0 39938450
2001 [Influence of human cytomegalovirus infection on the expressions of HOXB1, HOXB5, HOXB6, and HOXB9 genes in human embryo lung cells]. Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 0 12536675

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