ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle

Sep 24, 2026

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Breast cancer remains a leading cause of female cancer morbidity and mortality, yet effective targeted therapies are lacking for metastatic and triple-negative subtypes. ERCC6L, a key protein in chromosome separation during mitosis, has an unclear role in breast tumor development. The study finds ERCC6L is highly expressed in breast cancer, especially TNBC, correlating with poor patient outcomes. Mechanistically, ERCC6L accelerates the cell cycle via G2/M checkpoint signaling and promotes malignant behaviors through ERCC6L–KIF4A interaction.

LanguageEnglish

CategoryResearch & Report

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Reading Time43 min

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Abstract

Background

Methods and results

Conclusions

Introduction

Yang et al. Journal of Experimental & Clinical Cancer Research (2023) 42:227 [https://doi.org/10.1186/s13046-023-02806-x](https://doi.org/10.1186/s13046-023-02806-x) Journal of Experimental & Clinical Cancer Research RESEARCH Open Access ERCC6L facilitates the onset of mammary neoplasia and promotes the high malignance of breast cancer by accelerating the cell cycle Hong Yang1,2†, Xiangjin Zhen1,2†, Yihui Yang1,2, Yizhi Zhang1,2, Sen Zhang1,2, Yue Hao1,2, Guanhua Du 1,2, Hongquan Wang3, Bailin Zhang4, Wan Li1,2* and Jinhua Wang1,2* Abstract Background Breast cancer (BC) is the leading cause of morbidity and the second leading cause of death among female malignant tumors. Although available drugs have been approved for the corresponding breast cancer subtypes (ER-positive, HER2+) currently, there are still no effective targeted drugs or treatment strategies for metastatic breast cancer or triple-negative breast cancer that lack targets. Therefore, it is urgent to discover new potential targets. ERCC6L is an essential protein involved in chromosome separation during cell mitosis. However, the effect of ERCC6Lon the tumorigenesis and progression of breast cancer is unclear. Methods and results Here, we found that ERCC6L was highly expressed in breast cancer, especially inTNBC, which was closely related to poor outcomes of patients. An ERCC6L conditional knockout mouse model was first established in this study, and the results confirmed that ERCC6L was required for the development of the mammary gland and the tumorigenesis and progression of mammary gland cancers. In in vitro cell culture, ERCC6L acted as a tumor promoter in the malignant progression of breast cancer cells. Overexpression of ERCC6L promoted cell proliferation, migration and invasion, while knockdown of ERCC6L caused the opposite results. Mechanistically, ERCC6L accelerated the cell cycle by regulating the G2/M checkpoint signalling pathway. Additionally, we demonstrated that there is an interaction between ERCC6L and KIF4A, both of which are closely related factors in mitosis and are involved in the malignant progression of breast cancer. Conclusions We first demonstrated that ERCC6L deficiency can significantly inhibit the occurrence and development of mammary gland tumors. ERCC6L was found to accelerate the cell cycle by regulating the p53/p21/ CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B signalling pathways, thereby promoting the malignant progression of breast cancer cell lines. There was a direct interaction between KIF4A and ERCC6L, and both are closely associated with mitosis and contribute to growth and metastasis of breast tumor. To sum up, our results suggest that ERCC6L may be used as a promising target for the treatment of BC. †Hong Yang and Xiangjin Zhen contributed equally to this work. *Correspondence: Wan Li[liwan@imm.ac.cn](liwan@imm.ac.cn)[ ](liwan@imm.ac.cn)Jinhua Wang [wjh@imm.ac.cn](wjh@imm.ac.cn) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.

FAQs

What is ERCC6L’s role in breast cancer according to this study?

ERCC6L is highly expressed in breast cancer, particularly in TNBC, and supports tumor initiation and malignant progression by accelerating the cell cycle. Loss or suppression of ERCC6L inhibits these processes.

How did researchers test ERCC6L function in vivo and in vitro?

They established an ERCC6L conditional knockout mouse model to assess mammary gland tumor development, and they used cell culture experiments to measure proliferation, migration, and invasion after ERCC6L overexpression or knockdown.

Which signaling pathway is linked to ERCC6L-mediated cell-cycle acceleration?

ERCC6L was shown to accelerate the cell cycle by regulating the G2/M checkpoint signaling pathway, including p53/p21/CDK1/Cyclin B and PLK/CDC25C/CDK1/Cyclin B.

Sep 24, 2026

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