{
  "abstract": "Background\n\nAdriamycin 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\n\nClinical 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\n\nMCOLN2 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\n\nThe 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Biological Resource Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.",
    "School of Biomedical Sciences and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.",
    "Department of Radiation Oncology, Dalian Municipal Central Hospital, Dalian, China.",
    "College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.",
    "Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat- sen University, Guangzhou, China.",
    "National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou, China.",
    "Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.",
    "Centre for Cell & Developmental Biology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.",
    "Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. mengxq3@mail.sysu.edu.cn.",
    "Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. mengxq3@mail.sysu.edu.cn.",
    "School of Biomedical Sciences and Li Ka Shing Institute of Health Science, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. yao2068@cuhk.edu.hk.",
    "Centre for Cell & Developmental Biology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China. yao2068@cuhk.edu.hk."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongyan Yu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jie Wang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yongchen Ji"
    },
    {
      "affs": [
        4
      ],
      "name": "Xiaofang Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingxu Xie"
    },
    {
      "affs": [
        1
      ],
      "name": "Chun Yin Lo"
    },
    {
      "affs": [
        5
      ],
      "name": "Wenhan Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Huazhong Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoxue Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Xiaoling Huang"
    },
    {
      "affs": [
        7
      ],
      "name": "Liwen Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoqiong Gu"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Xiangqi Meng"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Xiaoqiang Yao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0kx2e5b3y3wpv.bib",
  "cited_by": 0,
  "doi": "10.1007/s13402-026-01270-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13719976",
  "id": "0kx2e5b3y3wpv",
  "issns": [
    "2211-3428",
    "2211-3436"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957906",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7172281299",
  "pdf_url": "https://europepmc.org/articles/PMC13719976?pdf=render",
  "pmcid": "PMC13719976",
  "pmid": "42957906",
  "published": "2026-08-03",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/0kx2e5b3y3wpv.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:29Z",
      "native_id": "MED:42957906",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957906"
    },
    {
      "first_seen": "2026-11-02T12:23:50Z",
      "native_id": "PMC13719976",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s13402-026-01270-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "MCOLN2 (Mucolipin-2) promotes autophagy to confer Adriamycin resistance in breast cancer by regulating mTOR degradation.",
  "title_text": "MCOLN2 (Mucolipin-2) promotes autophagy to confer Adriamycin resistance in breast cancer by regulating mTOR degradation.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:56Z",
  "url": "https://research.draconitic.com/paper/0kx2e5b3y3wpv",
  "venue": "Cellular oncology (Dordrecht, Netherlands)",
  "versions": []
}