Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Apr 11;11(2):701-710.
doi: 10.1016/j.gendis.2023.03.012. eCollection 2024 Mar.

The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities

Minjie Wu  1   2 , Heng Dong  1   2 , Chao Xu  1   2 , Mengqing Sun  1   2 , Haojin Gao  1   2 , Fangtian Bu  1   2 , Jianxiang Chen  1   3   2
Affiliations
Review

The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities

Minjie Wu et al. Genes Dis. .

Abstract

B-cell CLL/lymphoma 9 (BCL9) is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types, mainly through potentiating the Wnt/β-catenin signaling. However, increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles. Herein, we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular, physiological, or pathological processes. Moreover, we also concluded that the targeted inhibitors disrupt the interaction of β-catenin with BCL9 reported recently.

Keywords: BCL9; Development; Immunity; Multifaceted functions; Therapeutic target; Tumorigenesis.

PubMed Disclaimer

Figures

Fig. 1
Figure 1
BCL9 functions as a Wnt coactivator. (A) BCL9 functions as a coactivator of Wnt/β-catenin dependent transcription. BCL9 functions by recruiting the transcriptional coactivator PYGO to the β-catenin/TCF complex, which is required for the transcription of Wnt target genes. (B) The specific domains of BCL9 interact with PYGO and β-catenin.
Fig. 2
Figure 2
The diverse mechanisms of BCL9 independent of canonical Wnt-signaling. (A) BCL9 competes with Clathrin to promote mitotic Wnt/STOP. (B) BCL9 and Hippo signaling pathway. (C) BCL9 interacts with paraspeckle proteins and microRNAs.
Fig. 3
Figure 3
BCL9 is involved in the modulation of the tumor microenvironment. (A) The BCL9-STAT3 axis drives cancer progression and invasion. (B) BCL9 regulates immune cell infiltration in tumor cells.
Fig. 4
Figure 4
The diagram of BCL9 and the drugs target BCL9.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Willis T.G., Zalcberg I.R., Coignet L.J.A., et al. Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21. Blood. 1998;91(6):1873–1881. - PubMed
    1. Chan C.J., Martinet L., Gilfillan S., et al. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 2014;15(5):431–438. - PubMed
    1. Gay D.M., Ridgway R.A., Müller M., et al. Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer. Nat Commun. 2019;10:723. - PMC - PubMed
    1. Feng M., Wu Z., Zhou Y., et al. BCL9 regulates CD226 and CD96 checkpoints in CD8+ T cells to improve PD-1 response in cancer. Signal Transduct Targeted Ther. 2021;6:313. - PMC - PubMed
    1. Zhang Y., Zhang Q., Chen H., et al. BCL9 promotes epithelial mesenchymal transition and invasion in cisplatin resistant NSCLC cells via β-catenin pathway. Life Sci. 2018;208:284–294. - PubMed

LinkOut - more resources