B cell CLL/lymphoma 10 promotes colorectal cancer cell proliferation and regulates cuproptosis sensitivity through the NF-κB signaling pathway

doi:10.3748/wjg.v31.i34.109825

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Sep 14, 2025; 31(34): 109825
Published online Sep 14, 2025. doi: 10.3748/wjg.v31.i34.109825

B cell CLL/lymphoma 10 promotes colorectal cancer cell proliferation and regulates cuproptosis sensitivity through the NF-κB signaling pathway

Peng-Tuo Xiao, Chang-Feng Li, Yuan-Da Liu, Jing Zhong, Xi-Lun Cui, Chang Liu, Wei Yang

Peng-Tuo Xiao, Chang-Feng Li, Yuan-Da Liu, Xi-Lun Cui, Chang Liu, Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China

Jing Zhong, Medical Imaging Center, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 13000, Jilin Province, China

Wei Yang, Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130000, Jilin Province, China

Co-corresponding authors: Chang-Feng Li and Wei Yang.

Author contributions: Xiao PT contributed to conceptualization, data curation, investigation, software, writing - original draft. Li CF contributed to funding acquisition, project administration, resources, writing - review & editing. Liu YD and Zhong J contributed to formal analysis. Cui XL contributed to methodology. Liu C contributed to validation. Yang W contributed to project administration, resources, supervision, writing - review & editing. Both Li CF and Yang W have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Li CF applied for and obtained the funds for this research project. Yang W conceptualized, designed, and supervised the whole process of the project. She searched the literature, revised and submitted the early version of the manuscript with the focus on the association between BCL10 and DLAT. Li CF was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript. This collaboration between Li CF and Yang W is crucial for the publication of this manuscript and other manuscripts still in preparation.

Supported by the National Natural Science Foundation of China, No. 82073299; and Special Project for Health Research Talents of Jilin Province, No. 2023SCZ25.

Institutional animal care and use committee statement: All procedures were approved by the Ethics Committee on Animal Research of the Jilin University (Approval number: 2024425), the Institutional Guidelines on Animal Experimentation at Jilin University.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: All relevant data are included in the manuscript. Materials, data, and protocols described within the paper are available upon reasonable request to the corresponding authors.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Chang-Feng Li, Chief Physician, Postdoc, Professor, Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130000, Jilin Province, China. cfli@jlu.edu.cn

Received: May 23, 2025
Revised: June 29, 2025
Accepted: August 5, 2025
Published online: September 14, 2025
Processing time: 105 Days and 16.7 Hours

Abstract

BACKGROUND

Colorectal cancer (CRC) is a major global health burden. B cell CLL/lymphoma 10 (BCL10), a key component of the caspase recruitment domain protein-BCL10-mucosa-associated lymphoid tissue lymphoma paracaspase complexes, is upregulated in CRC and associated with poor patient prognosis, suggesting its potential role in CRC development and progression. Cuproptosis, a novel form of programmed cell death, has emerged as a promising therapeutic strategy for cancer.

AIM

To explore the role of BCL10 in regulating the sensitivity of CRC cells to cuproptosis.

METHODS

A series of in vitro and in vivo experiments were conducted using CRC cell lines and CRC mouse models to evaluate the effects of BCL10 on CRC cell proliferation, migration, invasion, and sensitivity to copper-induced cell death. Mechanistic studies were performed to elucidate the underlying molecular pathways.

RESULTS

BCL10 promoted CRC cell proliferation, migration, and invasion, while its knockdown had the opposite effects. BCL10 also influenced the sensitivity of CRC cells to cuproptosis, with BCL10 overexpression enhancing resistance and its knockdown increasing sensitivity. The mechanism involved BCL10 modulating the expression of DLAT, a key protein in the copper-induced cell death pathway, through activation of the nuclear factor kappa-B (NF-κB) signaling pathway.

CONCLUSION

BCL10 promotes CRC growth and regulates the sensitivity of CRC cells to cuproptosis by activating the NF-κB signaling pathway and modulating DLAT expression. These findings provide a molecular basis for developing BCL10-targeted therapies for CRC.

Keywords: Colorectal cancer; Nuclear factor kappa-B; Cuproptosis; B cell CLL/lymphoma 10; Cell death

Core Tip: B cell CLL/lymphoma 10 (BCL10) drives colorectal cancer (CRC) progression by promoting tumor cell proliferation, migration, and invasion, correlating with poor prognosis. It modulates CRC sensitivity to copper-induced cell death (cuproptosis), with overexpression increasing resistance and knockdown enhancing susceptibility. BCL10 activates nuclear factor kappa-B (NF-κB), suppressing DLAT-a key cuproptosis mediator. BCL10 knockdown increases DLAT oligomerization, boosting cuproptosis, while overexpression protects cells. Targeting BCL10 or the NF-κB-DLAT axis may improve CRC treatment by enhancing cuproptosis sensitivity. In vivo studies show BCL10 knockdown improves tumor response to copper therapy, supporting its therapeutic potential. These findings reveal BCL10 as a key CRC regulator, offering new treatment strategies.