Affinage

BCL9

B-cell CLL/lymphoma 9 protein · UniProt O00512

Length
1426 aa
Mass
149.3 kDa
Annotated
2026-06-09
95 papers in source corpus 23 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCL9 is an obligate adaptor protein of the nuclear Wnt/β-catenin transcriptional machinery, physically linking the chromatin reader Pygopus to nuclear β-catenin and thereby licensing activation of TCF/LEF target genes (PMID:11955446). Structurally, its HD2 domain forms an α-helix that contacts the first armadillo repeat of β-catenin—a site distinct from the cadherin/α-catenin interface—while its HD1 domain assembles with the Pygo PHD finger to decode H3K4-methylated histones, an interaction required for Wnt output (PMID:17052462, PMID:18498752). Within the Wnt enhanceosome, the BCL9/B9L C-terminus binds the Groucho/TLE co-repressor and the LDB1–SSBP enhanceosome core, with β-catenin docking triggering a rearrangement that apposes the C-terminus to TCF; the Pygo NPF motif anchors BCL9-Pygo to a single LDB1-SSBP2 complex that binds two Pygo molecules (PMID:28296634, PMID:37349336). BCL9 promotes β-catenin-driven transcription of oncogenic and stem-cell/EMT programs (c-Myc, cyclin D1, CD44, VEGF), and conditional ablation in mouse intestine and liver abrogates β-catenin-driven transformation and EMT while sparing broader Wnt responses, defining BCL9 as a context-selective β-catenin cofactor (PMID:19738061, PMID:20682801, PMID:30760720, PMID:30760710). This selectivity extends to development, where BCL9/Pygo are required for a subset of cardiac and myogenic Wnt programs (PMID:19699733, PMID:30366904). BCL9 expression is induced by HIF-1α through promoter hypoxia-responsive elements, and disrupting the β-catenin–BCL9 interface with a stabilized HD2 α-helix peptide suppresses tumor growth, validating the interaction as a therapeutic target (PMID:22914623, PMID:27121066). Beyond canonical Wnt signaling, BCL9 stabilizes calcium-signaling and neural mRNAs via paraspeckle proteins independently of β-catenin (PMID:31911584), and CDK1 phosphorylates BCL9 at Thr172 during mitosis to sustain mitotic Wnt signaling by limiting clathrin-mediated LRP6 degradation (PMID:30217955).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2002 High

    Established the founding role of BCL9 as the molecular adaptor that recruits Pygopus to the β-catenin–TCF complex, answering how Pygo is brought into Wnt transcriptional control.

    Evidence Genetic epistasis in Drosophila (Legless), co-immunoprecipitation and domain mapping

    PMID:11955446

    Open questions at the time
    • Atomic basis of the β-catenin and Pygo contacts not yet resolved
    • Identity of additional C-terminal effectors unknown
  2. 2006 High

    Defined the atomic interface by which BCL9 binds β-catenin, showing the HD2 α-helix engages armadillo repeat 1 at a site distinct from cadherin/α-catenin, explaining how transcriptional and adhesive β-catenin pools are separated.

    Evidence X-ray crystallography (2.6 Å) of β-catenin/BCL9/Tcf-4 with structure-guided mutagenesis

    PMID:17052462

    Open questions at the time
    • Did not address how the interaction is regulated in vivo
    • Affinity/competition with other armadillo-repeat ligands not quantified
  3. 2008 High

    Showed that the BCL9 HD1 domain enables Pygo to read H3K4me2, converting the adaptor into part of a histone-decoding module required for Wnt output.

    Evidence PHD–HD1–H3K4me peptide crystal structures, ITC, Drosophila rescue genetics

    PMID:18498752

    Open questions at the time
    • Genomic targets of the histone-reading function not mapped
    • Mechanistic coupling between H3K4me reading and transcriptional activation unresolved
  4. 2004 Medium

    Tested how β-catenin's adhesive-versus-transcriptional switch is controlled, proposing that Tyr142 phosphorylation favors BCL9-2 over α-catenin binding to drive nuclear function.

    Evidence RNAi, Co-IP, phospho-site mutagenesis, zebrafish epistasis in carcinoma cells

    PMID:15371335

    Open questions at the time
    • The Tyr142 mechanism was contradicted by subsequent work (idx 4)
    • Single-lab finding
  5. 2006 Medium

    Demonstrated functional interchangeability of BCL9-2 with Drosophila Legless and showed Pygo binding is essential, while disputing the proposed importance of β-catenin Tyr142 phosphorylation.

    Evidence Drosophila rescue, mammalian reporter assays, Co-IP

    PMID:17113272

    Open questions at the time
    • Conflict with idx 3 on Tyr142 not reconciled within this study
    • Single lab
  6. 2008 Medium

    Established that BCL9 is required for β-catenin-mediated transcription in human Wnt-responsive and APC-mutant colorectal cells and identified an essential but uncharacterized C-terminal ligand, plus a Wnt-inducible feedback loop.

    Evidence RNAi, dominant-negative overexpression, TCF/LEF reporters in HEK293 and SW480 cells

    PMID:18627596

    Open questions at the time
    • Identity of the C-terminal ligand left unknown
    • Single lab; limited cell-line contexts
  7. 2008 Medium

    Located a C-terminal transcriptional activation domain in BCL9 that synergizes with β-catenin's transactivation domain and partly bypasses Pygo, linking BCL9 to histone-acetyltransferase coactivators.

    Evidence Luciferase reporters, deletion/mutation analysis, Co-IP in lymphoid and non-lymphoid lines

    PMID:18347063

    Open questions at the time
    • Direct BCL9–CBP/p300 binding inferred via β-catenin, not demonstrated independently
    • Pygo-independent activity not fully mapped to a domain
  8. 2009 Medium

    Connected BCL9 to oncogenic phenotypes in vivo, showing it drives proliferation, invasion, metastasis and angiogenesis through canonical Wnt target genes.

    Evidence RNAi/overexpression, migration/invasion assays, xenograft mouse models

    PMID:19738061

    Open questions at the time
    • Causality between specific targets and phenotype correlative
    • Single lab
  9. 2009 High

    Demonstrated a physiological requirement for BCL9/BCL9-2 in Wnt activation during muscle regeneration, linking the adaptor to nuclear β-catenin localization and differentiation.

    Evidence Cre-lox conditional knockout, RNAi, β-catenin immunofluorescence, reporter assays

    PMID:19699733

    Open questions at the time
    • Target genes governing myogenic differentiation not defined
    • Tissue specificity of requirement unexplained
  10. 2010 High

    Defined BCL9/BCL9l as selectively required for a Wnt-dependent stem-cell and EMT transcriptional program in intestine and adenocarcinoma, distinguishing it from global Wnt signaling.

    Evidence Intestine-specific conditional knockout, transcriptional profiling, histology

    PMID:20682801

    Open questions at the time
    • Molecular basis of program selectivity unresolved
    • Distinction from generic Wnt targets at the chromatin level not mapped
  11. 2012 High

    Provided pharmacological proof that the BCL9 HD2–β-catenin interface is essential and druggable, by using a stabilized α-helix to dissociate the complex and suppress tumor growth.

    Evidence Stabilized α-helix peptide, Co-IP disruption, reporter and xenograft models

    PMID:22914623

    Open questions at the time
    • Specificity for BCL9 over other armadillo ligands in vivo not exhaustively shown
    • Resistance mechanisms not explored
  12. 2013 Medium

    Identified an endogenous brake on BCL9 recruitment: LATS2 binds β-catenin and disrupts the β-catenin/BCL9 interaction independently of its kinase activity.

    Evidence Reciprocal Co-IP, ChIP on Wnt promoters, kinase-dead mutant analysis

    PMID:24360964

    Open questions at the time
    • Structural basis of LATS2 competition unknown
    • Single lab
  13. 2017 High

    Reframed BCL9/B9L as constitutive enhanceosome components, showing the C-terminus binds Groucho/TLE and the LDB1-SSDP core, with a Wnt-triggered rearrangement apposing it to TCF.

    Evidence CRISPR/Cas9 engineering, BioID proximity labeling, Co-IP across Drosophila and human cells

    PMID:28296634

    Open questions at the time
    • Structural detail of the C-terminus–TLE/core contacts not resolved here
    • How the activation switch is triggered mechanistically unclear
  14. 2017 Medium

    Linked hypoxia to Wnt coactivator dosage, showing HIF-1α (but not HIF-2α) directly induces BCL9 via promoter HREs in colorectal cancer.

    Evidence BCL9 promoter luciferase reporters with HRE mutation, HIF overexpression/siRNA, ChIP

    PMID:27121066

    Open questions at the time
    • Physiological contribution of hypoxic induction to tumor Wnt activity not quantified
    • Single lab
  15. 2017 Low

    Reported SOX7 as a competitive antagonist that displaces BCL9 from β-catenin to suppress oncogenic transcription.

    Evidence Co-IP, TCF/LEF reporters, competitive binding analysis

    PMID:29271667

    Open questions at the time
    • Single Co-IP and reporter assay without reciprocal/structural validation
    • Limited mechanistic follow-up; single lab
  16. 2018 Medium

    Uncovered a mitotic, cell-cycle-coupled regulation of BCL9 in which CDK1 phosphorylation at Thr172 limits clathrin-mediated LRP6 degradation to sustain mitotic Wnt signaling.

    Evidence Mitotic interactome MS, Co-IP, T172A phospho-mutant, cell division assays

    PMID:30217955

    Open questions at the time
    • Direct BCL9–clathrin contact and stoichiometry not fully defined
    • Single lab
  17. 2018 High

    Demonstrated tissue-selective β-catenin cofactor function by showing the β-catenin–BCL9–Pygo complex is specifically required for cardiac developmental Wnt programs while other Wnt responses persist.

    Evidence Combined Bcl9/Pygo mutants in zebrafish and mouse, cardiac gene expression analysis

    PMID:30366904

    Open questions at the time
    • Why cardiac targets depend selectively on BCL9/Pygo unresolved
    • Direct chromatin targets not enumerated
  18. 2019 High

    Showed genetically that BCL9/Bcl9l are required for β-catenin-driven intestinal and hepatic transformation and cooperate with Pygo to shift gene expression from stem-cell-like to secretory differentiation.

    Evidence ApcMin/Apc1322T conditional knockouts, genetic synergy with Pygo deletion, expression profiling

    PMID:30760710 PMID:30760720

    Open questions at the time
    • Mechanism linking BCL9/Pygo loss to Notch-driven differentiation not detailed
    • Selectivity over normal homeostatic Wnt incompletely explained
  19. 2020 Medium

    Identified a β-catenin-independent function for BCL9 in stabilizing calcium-signaling and neural mRNAs via paraspeckle proteins under calcium/stress signaling.

    Evidence Co-IP with paraspeckle proteins, RNA-IP, live-cell calcium imaging, siRNA in colorectal cancer cells

    PMID:31911584

    Open questions at the time
    • Direct RNA-binding versus indirect recruitment not distinguished
    • Single lab; novel mechanism not independently replicated
  20. 2020 Medium

    Extended BCL9's transcriptional partnerships beyond β-catenin by showing it co-occupies enhancers with phospho-S727 STAT3 to drive invasive DCIS target genes.

    Evidence ChIP-exo, RNA-seq, BCL9 siRNA in a PDX DCIS MIND model

    PMID:32352029

    Open questions at the time
    • Direct BCL9–STAT3 binding versus co-recruitment unresolved
    • Single lab
  21. 2023 High

    Resolved how BCL9-Pygo integrates into the enhanceosome core, showing a single LDB1-SSBP2 complex binds two Pygo NPF motifs in a deep groove and that LDB/Pygo loss impairs Wnt transcription.

    Evidence X-ray crystallography of Pygo2/LDB1/SSBP2, Co-IP, CRISPR knockouts with reporter assays

    PMID:37349336

    Open questions at the time
    • Stoichiometry and architecture of the full BCL9-containing enhanceosome not resolved
    • Dynamics of the Wnt-triggered rearrangement not captured structurally
  22. 2024 Low

    Reported a BCL9–Nrf2 interaction that modulates ferroptosis susceptibility in thyroid carcinoma, extending BCL9 into redox/cell-death control.

    Evidence Co-IP, siRNA knockdown, ferroptosis assays, xenograft model

    PMID:39291848

    Open questions at the time
    • Single Co-IP from one lab; interaction not independently replicated
    • Direct versus indirect effect on Nrf2 stability not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BCL9 achieves context- and tissue-selective Wnt target gene activation—and how its β-catenin-independent RNA-stabilizing, mitotic, and redox functions are integrated—remains unresolved.
  • No structure of the complete BCL9-containing enhanceosome on chromatin
  • Molecular determinant of program selectivity unknown
  • Relationship among the distinct β-catenin-independent activities uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1643685 Disease 2
Partners
CTNNB1LDB1NFE2L2PYGO2SSBP2STAT3TCF7L2TLE
Complex memberships
Pygo-BCL9-LDB1-SSBP core complexWnt enhanceosomeβ-catenin/BCL9/TCF complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 BCL9 (Drosophila ortholog Legless/Lgs) physically links Pygopus (Pygo) to nuclear β-catenin, thereby recruiting Pygo to the β-catenin–TCF complex and enabling Wnt transcriptional activation. Genetic and molecular (co-IP, epistasis) evidence established this adaptor function. Genetic epistasis in Drosophila, co-immunoprecipitation, domain mapping Cell High 11955446
2006 Crystal structure of a β-catenin/BCL9/Tcf-4 triple complex at 2.6 Å resolution revealed that BCL9's β-catenin-binding domain (CBD) forms an α-helix that contacts the first armadillo repeat of β-catenin — a site distinct from cadherin/α-catenin binding. Mutation of this armadillo repeat abolished BCL9 binding without disrupting cadherin interactions. X-ray crystallography (2.6 Å), structure-guided mutagenesis Molecular cell High 17052462
2008 The BCL9/Legless HD1 domain forms a ternary complex with the Pygo PHD finger to bind specifically to histone H3 methylated at lysine 4 (H3K4me2). HD1 association is required for efficient H3K4me binding, and this histone-decoding function is necessary for Wnt signaling outputs in Drosophila rescue experiments. Crystal structures of PHD–HD1–H3K4me peptide ternary complexes; ITC binding assays; Drosophila rescue genetics Molecular cell High 18498752
2004 BCL9-2 (B9L) binding to β-catenin modulates the switch between β-catenin's adhesive and transcriptional functions. Phosphorylation of Tyr142 of β-catenin favors BCL9-2 binding and precludes α-catenin interaction, thereby promoting nuclear (transcriptional) over membrane (adhesive) β-catenin function. RNAi of BCL9-2 in carcinoma cells induces epithelial phenotype and relocates β-catenin from nucleus to membrane. RNAi knockdown, co-immunoprecipitation, phosphorylation site mutagenesis, zebrafish epistasis Genes & development Medium 15371335
2006 BCL9-2 can functionally replace Drosophila Legless (BCL9) in vivo and in cultured cells, and this rescue requires the ability of BCL9-2 to bind Pygo; the Tyr142 phosphorylation of β-catenin was found not to be important for BCL9-2 recruitment or transcriptional activity in multiple assays. Drosophila in vivo rescue assays, mammalian cell transcriptional reporter assays, co-immunoprecipitation Mechanisms of development Medium 17113272
2008 BCL9 is required for efficient β-catenin-mediated transcription in Wnt-stimulated HEK293 cells and SW480 colorectal cancer cells (APC-mutant). BCL9 function depends on both its β-catenin-binding domain and an unknown C-terminal ligand. BCL9 and B9L/BCL9-2 are Wnt-inducible genes, indicating a positive feedback loop. RNAi knockdown, dominant-negative overexpression, TCF/LEF reporter assays in human cell lines BMC cancer Medium 18627596
2008 BCL9 contains a C-terminal transcriptional activation domain that functionally synergizes with β-catenin's C-terminal transactivation domain in lymphoid cells, and this activity is partially Pygopus-independent. The β-catenin transactivation domain associates with histone acetyltransferases CBP/p300 and TRRAP/GCN5. Luciferase reporter assays, deletion/mutation analysis, co-immunoprecipitation in lymphoid and non-lymphoid cell lines Molecular and cellular biology Medium 18347063
2009 BCL9 enhances β-catenin-mediated transcriptional activity and promotes proliferation, migration, invasion, and metastasis of tumor cells. BCL9 knockdown in xenograft models reduced tumor load, metastasis, and angiogenesis, accompanied by downregulation of c-Myc, cyclin D1, CD44, and VEGF. RNAi knockdown, overexpression, in vitro migration/invasion assays, xenograft mouse models Cancer research Medium 19738061
2009 BCL9 is required for Wnt/β-catenin cascade activation in adult myogenic progenitors; loss of BCL9/BCL9-2 (via Cre-lox deletion or RNAi) abrogates nuclear β-catenin localization and TCF/LEF-mediated transcription normally observed upon Wnt stimulation, and impairs myogenic differentiation and muscle regeneration. Cre-lox conditional knockout in mouse myogenic lineage, RNAi in vitro, β-catenin localization by immunofluorescence, TCF/LEF reporter assays Developmental biology High 19699733
2010 Conditional ablation of Bcl9/Bcl9l in mouse intestinal epithelium decreases intestinal stem cell marker expression and impairs colon regeneration. In Wnt-driven adenocarcinomas, loss of Bcl9/Bcl9l abrogates EMT and stem-cell-like transcriptional programs, demonstrating that BCL9/BCL9l are specifically required for a Wnt-dependent stem cell and EMT gene expression program. Conditional knockout mouse genetics (intestine-specific Cre), transcriptional profiling, histology Cancer research High 20682801
2012 A stabilized α-helix of BCL9 (SAH-BCL9) that mimics the BCL9 HD2 domain binds β-catenin, dissociates native β-catenin/BCL9 complexes, and selectively suppresses Wnt transcription. This peptide inhibitor suppresses tumor growth, angiogenesis, invasion, and metastasis in xenograft models, mechanistically validating BCL9 HD2-mediated direct binding to β-catenin as essential for oncogenic Wnt signaling. Stabilized α-helix peptide design, co-immunoprecipitation disruption assays, luciferase reporter, xenograft mouse models Science translational medicine High 22914623
2013 LATS2 inhibits oncogenic Wnt/β-catenin transcription by directly interacting with β-catenin and disrupting the β-catenin/BCL9 interaction, thereby blocking BCL9 recruitment to Wnt target gene promoters. This function is independent of LATS2 kinase activity. Co-immunoprecipitation, ChIP on Wnt target gene promoters, reporter assays, kinase-dead mutant analysis Cell reports Medium 24360964
2017 BCL9 and B9L (BCL9L) are constitutive components of the Wnt enhanceosome. CRISPR/Cas9 engineering and BioID proximity labeling showed that the C-terminus of BCL9/B9L (downstream of the adaptor elements) is required for Wnt responses. The BCL9/B9L C-terminus binds the Groucho/TLE co-repressor and also binds the Chip/LDB1-SSDP enhanceosome core complex via a conserved element. Upon Wnt-dependent β-catenin docking, a rearrangement apposes the BCL9/B9L C-terminus to TCF. CRISPR/Cas9 genome engineering, BioID proximity labeling, co-immunoprecipitation, domain deletion analysis in Drosophila and human cells eLife High 28296634
2017 HIF-1α transcriptionally induces BCL9 expression in human colorectal cancer cells via two functional hypoxia-responsive elements (HRE-B and HRE-C) in the BCL9 promoter. HIF-2α does not activate BCL9. This establishes a mechanistic link between hypoxia signaling and Wnt/β-catenin coactivator expression. BCL9 promoter luciferase reporter assays with HRE mutations, HIF-1α/2α overexpression and siRNA knockdown, ChIP Oncotarget Medium 27121066
2018 CDK1 phosphorylates BCL9 at Thr172 (N-terminal) during mitosis. This phosphorylation prevents clathrin-mediated degradation of LRP6 signalosome components by BCL9 interacting with clathrin and Wnt destruction complex components, thereby sustaining mitotic Wnt signaling and promoting precise cell division. Mitotic interactome analysis (MS), co-immunoprecipitation, phospho-site mutagenesis (T172A), cell division assays The EMBO journal Medium 30217955
2018 In zebrafish and mouse, disrupting the β-catenin–BCL9–Pygo complex by combined Bcl9/Pygo mutations causes congenital heart defects with broadly maintained canonical Wnt responses in other tissues, identifying BCL9 and Pygo as selective β-catenin cofactors for a subset of Wnt-dependent cardiac developmental programs. Zebrafish and mouse genetics (combined Bcl9/Pygo mutants), gene expression analysis of cardiac regulators Genes & development High 30366904
2019 Intestinal deletion of Bcl9/Bcl9l suppresses Wnt pathway deregulation following APC loss, reduces intestinal tumour growth (especially colonic), and completely abrogates β-catenin-driven intestinal and hepatocellular transformation. Loss of BCL9/9l also synergizes with Pygo loss to shift gene expression from stem-cell-like to Notch-regulated secretory differentiation in Apc-mutant adenomas. Conditional knockout mouse genetics (ApcMin and Apc1322T models), genetic rescue/synergy with Pygo deletion, gene expression profiling Nature communications High 30760710 30760720
2020 BCL9 has a β-catenin-independent function: in response to calcium transients or cellular stress, BCL9 is recruited to interchromosomal regions where it stabilizes mRNAs of calcium signaling and neural-associated genes by interacting with paraspeckle proteins, thereby sustaining neurotransmitter-dependent communication among colorectal cancer cells. Co-immunoprecipitation with paraspeckle proteins, RNA-IP, live-cell imaging of calcium transients, siRNA knockdown Nature communications Medium 31911584
2023 Crystal structure of a ternary complex comprising the N-terminus of human Pygo2, LDB1, and SSBP2 revealed that BCL9-Pygo assembles with the LDB-SSBP core complex via a conserved N-terminal NPF motif of Pygo2. A single LDB1-SSBP2 complex simultaneously binds two Pygo2 molecules through their NPF motifs, which dock into a deep groove between LDB1 and SSBP2. Loss of LDB or Pygo in human cell lines impairs Wnt/β-catenin-dependent transcription. X-ray crystallography, co-immunoprecipitation, CRISPR/Cas9 human cell line knockouts with reporter assays Nature communications High 37349336
2017 SOX7 inhibits oncogenic β-catenin-mediated transcription by competing with BCL9 to bind β-catenin, thereby disrupting the β-catenin/BCL9 interaction. Co-immunoprecipitation, TCF/LEF luciferase reporter assays, competitive binding analysis DNA and cell biology Low 29271667
2024 BCL9 interacts with Nrf2; BCL9 knockdown decreases Nrf2 expression and affects Nrf2 downstream target genes, inducing ferroptosis in thyroid carcinoma cells. Co-IP confirmed the BCL9–Nrf2 physical interaction. Co-immunoprecipitation, siRNA knockdown, ferroptosis assays, xenograft mouse model Molecular carcinogenesis Low 39291848
2020 BCL9 forms a complex with phosphoserine-727 STAT3 and non-STAT3 transcription factors on chromatin enhancers in DCIS cells. ChIP-exo showed BCL9-pS727-STAT3 co-occupancy at enhancers driving transcription of integrin β3 and MMP16, which mediate DCIS invasive progression. ChIP-exo, RNA sequencing, siRNA knockdown of BCL9 in PDX DCIS MIND model NPJ breast cancer Medium 32352029

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 490 11955446
2004 Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions. Genes & development 273 15371335
2012 Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling. Science translational medicine 221 22914623
2012 Design of triazole-stapled BCL9 α-helical peptides to target the β-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction. Journal of medicinal chemistry 186 22196480
2006 Crystal structure of a beta-catenin/BCL9/Tcf4 complex. Molecular cell 171 17052462
2009 BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells. Cancer research 164 19738061
2014 miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/β-catenin/BCL9 pathway. Cancer research 162 24599134
2008 Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex. Molecular cell 145 18498752
1998 Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21. Blood 138 9490669
2010 Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas. Cancer research 109 20682801
2016 MEF2D-BCL9 Fusion Gene Is Associated With High-Risk Acute B-Cell Precursor Lymphoblastic Leukemia in Adolescents. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 97 27507882
2008 The function of BCL9 in Wnt/beta-catenin signaling and colorectal cancer cells. BMC cancer 97 18627596
2019 Pharmacological inhibition of β-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells. Science advances 95 31086813
2009 BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration. Developmental biology 79 19699733
2004 Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling. Cancer research 79 15574752
2017 Hypoxia activates Wnt/β-catenin signaling by regulating the expression of BCL9 in human hepatocellular carcinoma. Scientific reports 77 28074862
2017 Constitutive scaffolding of multiple Wnt enhanceosome components by Legless/BCL9. eLife 74 28296634
2019 Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nature communications 71 30760720
2017 miR-1301 inhibits hepatocellular carcinoma cell migration, invasion, and angiogenesis by decreasing Wnt/β-catenin signaling through targeting BCL9. Cell death & disease 65 28817119
2013 LATS2 suppresses oncogenic Wnt signaling by disrupting β-catenin/BCL9 interaction. Cell reports 59 24360964
2017 miR-30a acts as a tumor suppressor by double-targeting COX-2 and BCL9 in H. pylori gastric cancer models. Scientific reports 55 28769030
2011 MicroRNA-30c-2* expressed in ovarian cancer cells suppresses growth factor-induced cellular proliferation and downregulates the oncogene BCL9. Molecular cancer research : MCR 54 22024689
2008 Cell-type-specific function of BCL9 involves a transcriptional activation domain that synergizes with beta-catenin. Molecular and cellular biology 49 18347063
2015 BCL9/9L-β-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer. EBioMedicine 48 26844272
2011 BCL9-2 promotes early stages of intestinal tumor progression. Gastroenterology 47 21703997
2022 Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis. Cell death discovery 41 35368023
2021 miR-140-3p inhibits colorectal cancer progression and its liver metastasis by targeting BCL9 and BCL2. Cancer medicine 41 33838016
2013 BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies. PloS one 41 23382809
2018 Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/β-catenin signaling. Genes & development 37 30366904
2022 miRNA-122-5p in POI ovarian-derived exosomes promotes granulosa cell apoptosis by regulating BCL9. Cancer medicine 36 35229987
2021 BCL9/BCL9L promotes tumorigenicity through immune-dependent and independent mechanisms in triple negative breast cancer. Oncogene 35 33767438
2011 Common variants in the BCL9 gene conferring risk of schizophrenia. Archives of general psychiatry 34 21383261
2021 BCL9 regulates CD226 and CD96 checkpoints in CD8+ T cells to improve PD-1 response in cancer. Signal transduction and targeted therapy 33 34417435
2020 BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins. Nature communications 33 31911584
2009 Analysis of the interaction of BCL9 with beta-catenin and development of fluorescence polarization and surface plasmon resonance binding assays for this interaction. Biochemistry 32 19715304
2006 BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling. Mechanisms of development 32 17113272
2022 A novel β-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer. Science advances 31 35486727
2019 LncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 30909141
2019 Wnt status-dependent oncogenic role of BCL9 and BCL9L in hepatocellular carcinoma. Hepatology international 30 31440992
2016 BCL9, a coactivator for Wnt/β-catenin transcription, is targeted by miR-30c and is associated with prostate cancer progression. Oncology letters 30 26998113
2019 Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models. Nature communications 28 30760710
2021 The interactions of Bcl9/Bcl9L with β-catenin and Pygopus promote breast cancer growth, invasion, and metastasis. Oncogene 24 34545187
2019 MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/β-catenin signaling through targeting BCL9. Artificial cells, nanomedicine, and biotechnology 24 31561723
2018 BCL9 promotes epithelial mesenchymal transition and invasion in cisplatin resistant NSCLC cells via β-catenin pathway. Life sciences 24 30009824
2018 MiR-532 downregulation of the Wnt/β-catenin signaling via targeting Bcl-9 and induced human intervertebral disc nucleus pulposus cells apoptosis. Journal of pharmacological sciences 24 30472057
2018 CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling. The EMBO journal 23 30217955
2022 Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9. Scientific reports 21 35027586
2024 Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell (cDC1) activation and tumor infiltration. Signal transduction and targeted therapy 20 38811552
2018 MicroRNA-1301 inhibits migration and invasion of osteosarcoma cells by targeting BCL9. Gene 20 30172867
2017 SOX7 Suppresses Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction. DNA and cell biology 20 29271667
2021 LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/β-catenin signaling. Environmental toxicology 19 33974352
2019 Long non-coding RNA NNT-AS1 functions as an oncogenic gene through modulating miR-485/BCL9 in cholangiocarcinoma. Cancer management and research 19 31616187
2014 The BCL9-2 proto-oncogene governs estrogen receptor alpha expression in breast tumorigenesis. Oncotarget 19 25149534
2019 Targeted disruption of the BCL9/β-catenin interaction by endosomal-escapable nanoparticles functionalized with an E-cadherin-derived peptide. Nanotechnology 18 31751960
2021 Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR-30a to regulate COX-2/BCL9 pathway. Helicobacter 17 34396632
2021 Circular RNA circFNDC3AL Upregulates BCL9 Expression to Promote Chicken Skeletal Muscle Satellite Cells Proliferation and Differentiation by Binding to miR-204. Frontiers in cell and developmental biology 17 34660593
2020 BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression. NPJ breast cancer 17 32352029
2007 Up-regulation of a BCL9-related beta-catenin-binding protein, B9L, in different stages of sporadic colorectal adenoma. Cancer science 15 17129358
2021 Inhibition of BCL9 Modulates the Cellular Landscape of Tumor-Associated Macrophages in the Tumor Immune Microenvironment of Colorectal Cancer. Frontiers in pharmacology 14 34566638
2018 BCL9 Upregulation in Adrenocortical Carcinoma: A Novel Wnt/β-Catenin Activating Event Driving Adrenocortical Malignancy. Journal of the American College of Surgeons 14 29428231
2017 HIF-1α activates hypoxia-induced BCL-9 expression in human colorectal cancer cells. Oncotarget 14 27121066
2017 Aristaless Related Homeobox (ARX) Interacts with β-Catenin, BCL9, and P300 to Regulate Canonical Wnt Signaling. PloS one 14 28103279
2015 The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells. Molecular cancer research : MCR 13 25678599
2016 Differentially expressed microRNA-218 modulates the viability of renal cell carcinoma by regulating BCL9. Molecular medicine reports 12 27314976
2021 LncRNA MNX1-AS1 Contributes to Laryngeal Squamous Cell Carcinoma Growth and Migration by Regulating mir-744-5p/bcl9/β-Catenin Axis. Cell transplantation 11 33821684
2023 Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome. Nature communications 10 37349336
2021 Pharmacological Inhibition and Genetic Knockdown of BCL9 Modulate the Cellular Landscape of Cancer-Associated Fibroblasts in the Tumor-Immune Microenvironment of Colorectal Cancer. Frontiers in oncology 10 34026600
2019 MiR-30c exerts tumor suppressive functions in colorectal carcinoma by directly targeting BCL9. European review for medical and pharmacological sciences 10 31081087
2019 Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells. Cancer cell international 10 31827404
2024 Decoding the dynamics of BCL9 triazole stapled peptide. Biophysical chemistry 8 38335808
2023 The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities. Genes & diseases 8 37692512
2022 New ZW4864 Derivatives as Small-Molecule Inhibitors for the β-Catenin/BCL9 Protein-Protein Interaction. ACS medicinal chemistry letters 8 35586435
2021 Bcl9 Depletion Modulates Endothelial Cell in Tumor Immune Microenvironment in Colorectal Cancer Tumor. Frontiers in oncology 8 33552975
2022 Turning a Targeting β-Catenin/Bcl9 Peptide Inhibitor into a GdOF@Au Core/Shell Nanoflower for Enhancing Immune Response to Cancer Therapy in Combination with Immune Checkpoint Inhibitors. Pharmaceutics 7 35745877
2021 Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer. Pathology, research and practice 7 33862557
2015 Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population. Scientific reports 7 26494551
2006 Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells. BMC cancer 7 17020613
2021 Recent advances in β-catenin/BCL9 protein-protein interaction inhibitors. Future medicinal chemistry 5 33849283
2025 Targeting tumor-intrinsic BCL9 reverses immunotherapy resistance by eliciting macrophage-mediated phagocytosis and antigen presentation. Nature communications 4 41249197
2023 Modulating β-catenin/BCL9 interaction with cell-membrane-camouflaged carnosic acid to inhibit Wnt pathway and enhance tumor immune response. Frontiers in immunology 4 37881428
2021 Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma. Acta histochemica et cytochemica 4 35023882
2018 Expression of miR-30c and BCL-9 in gastric carcinoma tissues and their function in the development of gastric cancer. Oncology letters 4 30013632
2025 BCL9 as a Key Player in Wnt/β-catenin Signaling: Implications for Osteogenesis, Tissue Repair, and Oncology. Applied biochemistry and biotechnology 2 41222773
2024 BCL9 is a Risk Factor of Neck Lymph Nodes Metastasis and Correlated with Immune Cell Infiltration in Papillary Thyroid Carcinoma. International journal of general medicine 2 38645401
2022 The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients. Journal, genetic engineering & biotechnology 2 34978646
2015 [Association of BCL9 expression with prostate cancer clinicopathological features and survival]. Zhonghua yi xue za zhi 2 26711608
2025 GATA1-mediated Notch signaling augment antitumor immunity of CD11b+CD27- natural killer cells maturation via BCL9/β-catenin signal. Cell reports 1 40366806
2024 Dysregulated BCL9 Controls Tumorigenicity and Ferroptosis Susceptibility by Binding With Nrf2 in Thyroid Carcinoma. Molecular carcinogenesis 1 39291848
2021 MEF2D-BCL9 B-Lymphoblastic Leukemia Blast Morphology Does Not Always Mimic Mature B-Cell Leukemia. Journal of pediatric hematology/oncology 1 33235148
2019 Immunohistochemical Mapping of Bcl9 Using Two Antibodies that Recognize Different Epitopes Is Useful to Characterize Juvenile Development of Hepatocellular Carcinoma in Myanmar. Acta histochemica et cytochemica 1 30923411
2026 The GC-derived exosomal LncRNA DARS-AS1 activates Wnt/β-catenin pathway to drive angiogenesis by regulating miR-605-5p/BCL9. Journal of cancer research and clinical oncology 0 41563498
2026 Disruption of BCL9-β-catenin interaction by de novo designed miniproteins inhibits oncogenic signaling. International journal of biological macromolecules 0 42190771
2025 CD5-positive B-cell acute lymphoblastic leukemia/lymphoma with MEF2D::BCL9 mimicking aggressive mature B-cell lymphoma: a case report of a newly described entity and potential diagnostic pitfall. Journal of hematopathology 0 40358810
2025 LINC01232 regulates miR-516a-5p/BCL9 axis to promote triple-negative breast cancer progression. Cellular and molecular biology (Noisy-le-Grand, France) 0 40736291
2025 Disrupting β-Catenin/BCL9 interaction with a peptide prodrug boosts immunotherapy in colorectal cancer. Frontiers in immunology 0 40948801

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