MCOLN2 (Mucolipin-2) promotes autophagy to confer Adriamycin resistance in breast cancer by regulating mTOR degradation.
12 affiliations
- 1Department of Clinical Biological Resource Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
- 2School of Biomedical Sciences and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
- 3Department of Radiation Oncology, Dalian Municipal Central Hospital, Dalian, China.
- 4College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
- 5Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat- sen University, Guangzhou, China.
- 6National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou, China.
- 7Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- 8Centre for Cell & Developmental Biology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
- 9Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. [email protected].
- 10Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. [email protected].
- 11School of Biomedical Sciences and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. [email protected].
- 12Centre for Cell & Developmental Biology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China. [email protected].
Abstract
Background
Adriamycin is a cornerstone chemotherapeutic agent for advanced breast cancer, but its efficacy is frequently compromised by chemoresistance, a process in which macroautophagy is critically involved. However, the underlying mechanisms driving this autophagy-mediated resistance remain poorly understood.Methods
Clinical data from patients with breast cancer who underwent chemotherapy were collected and the expression of MCOLN2 in tumor tissues was assessed. Using Adriamycin-resistant MCF-7/ADM cells and their parental MCF-7 cells, we investigated the role of MCOLN2 in regulating autophagic flux and mediating drug resistance. Key findings were further validated using an in vivo xenograft model.Results
MCOLN2 expression was significantly upregulated in Adriamycin-resistant MCF-7/ADM cells and chemoresistant patient samples, where high levels correlated with poor prognosis. Knockdown of MCOLN2 sensitized MCF-7/ADM cells to Adriamycin both in vitro and in vivo, whereas its overexpression conferred resistance in parental MCF-7 cells. Mechanistically, MCOLN2 promoted autophagy, as evidenced by increased LC3-II levels and autophagosome formation. This pro-autophagic effect was mediated by MCOLN2-induced destabilization and lysosomal degradation of mTOR. Consequently, pharmacological or genetic inhibition of autophagy effectively reversed the MCOLN2-driven chemoresistance.Conclusion
The MCOLN2-mTOR-autophagy axis has a critical role in the development of therapeutic resistance to Adriamycin in breast cancer. Targeting MCOLN2 could be a promising therapeutic strategy to overcome Adriamycin resistance in breast cancer patients.
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BibTeX
@article{yu2026mcoln2,
title = {{MCOLN2 (Mucolipin-2) promotes autophagy to confer Adriamycin resistance in breast cancer by regulating mTOR degradation.}},
author = {Hongyan Yu and Jie Wang and Yongchen Ji and Xiaofang Liu and Mingxu Xie and Chun Yin Lo and Wenhan Cao and Huazhong Zhou and Xiaoxue Li and Xiaoling Huang and Liwen Jiang and Xiaoqiong Gu and Xiangqi Meng and Xiaoqiang Yao},
journal = {Cellular oncology (Dordrecht, Netherlands)},
year = {2026},
month = aug,
doi = {10.1007/s13402-026-01270-x},
url = {https://europepmc.org/article/MED/42957906},
note = {CC BY},
}
RIS
TY - JOUR
TI - MCOLN2 (Mucolipin-2) promotes autophagy to confer Adriamycin resistance in breast cancer by regulating mTOR degradation.
AU - Hongyan Yu
AU - Jie Wang
AU - Yongchen Ji
AU - Xiaofang Liu
AU - Mingxu Xie
AU - Chun Yin Lo
AU - Wenhan Cao
AU - Huazhong Zhou
AU - Xiaoxue Li
AU - Xiaoling Huang
AU - Liwen Jiang
AU - Xiaoqiong Gu
AU - Xiangqi Meng
AU - Xiaoqiang Yao
PY - 2026
DA - 2026/08/03
JO - Cellular oncology (Dordrecht, Netherlands)
DO - 10.1007/s13402-026-01270-x
UR - https://europepmc.org/article/MED/42957906
AB - Background Adriamycin is a cornerstone chemotherapeutic agent for advanced breast cancer, but its efficacy is frequently compromised by chemoresistance, a process in which macroautophagy is critically involved. However, the underlying mechanisms driving this autophagy-mediated resistance remain poorly understood.Methods Clinical data from patients with breast cancer who underwent chemotherapy were collected and the expression of MCOLN2 in tumor tissues was assessed. Using Adriamycin-resistant MCF-7/ADM cells and their parental MCF-7 cells, we investigated the role of MCOLN2 in regulating autophagic flux and mediating drug resistance. Key findings were further validated using an in vivo xenograft model.Results MCOLN2 expression was significantly upregulated in Adriamycin-resistant MCF-7/ADM cells and chemoresistant patient samples, where high levels correlated with poor prognosis. Knockdown of MCOLN2 sensitized MCF-7/ADM cells to Adriamycin both in vitro and in vivo, whereas its overexpression conferred resistance in parental MCF-7 cells. Mechanistically, MCOLN2 promoted autophagy, as evidenced by increased LC3-II levels and autophagosome formation. This pro-autophagic effect was mediated by MCOLN2-induced destabilization and lysosomal degradation of mTOR. Consequently, pharmacological or genetic inhibition of autophagy effectively reversed the MCOLN2-driven chemoresistance.Conclusion The MCOLN2-mTOR-autophagy axis has a critical role in the development of therapeutic resistance to Adriamycin in breast cancer. Targeting MCOLN2 could be a promising therapeutic strategy to overcome Adriamycin resistance in breast cancer patients.
SN - 2211-3428
SN - 2211-3436
ER -