2. Academic Validation
  3. The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization

The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization

  • Cell Death Dis. 2022 Oct 26;13(10):899. doi: 10.1038/s41419-022-05345-z.
Quanfu Li # 1 2,  Yunkai Chu # 1,  Shengze Li # 1,  Liping Yu 3,  Huayun Deng 1,  Chunhua Liao 1,  Xiaodong Liao 1,  Chihyu Yang 1,  Min Qi 3,  Jinke Cheng 1,  Guoqiang Chen 1,  Lei Huang 4
Affiliations

Affiliations

  • 1 Department of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
  • 3 Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.
  • 4 Department of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China. leihuang@shsmu.edu.cn.
  • # Contributed equally.
PMID: 36289190 DOI: 10.1038/s41419-022-05345-z
Abstract

Mitophagy is a vital process that controls mitochondria quality, dysregulation of which can promote Cancer. Oncoprotein Mucin 1 (MUC1) targets mitochondria to attenuate drug-induced Apoptosis. However, little is known about whether and how MUC1 contributes to mitochondrial homeostasis in Cancer cells. We identified a novel role of MUC1 in promoting Mitophagy. Increased Mitophagy is coupled with the translocation of MUC1 to mitochondria, where MUC1 interacts with and induces degradation of ATPase family AAA domain-containing 3A (ATAD3A), resulting in protection of PTEN-induced kinase 1 (Pink1) from ATAD3A-mediated cleavage. Interestingly, MUC1-induced Mitophagy is associated with increased oncogenicity of Cancer cells. Similarly, inhibition of Mitophagy significantly suppresses MUC1-induced Cancer cell activity in vitro and in vivo. Consistently, MUC1 and ATAD3A protein levels present an inverse relationship in tumor tissues of breast Cancer patients. Our data validate that MUC1/ATAD3A/Pink1 axis-mediated Mitophagy constitutes a novel mechanism for maintaining the malignancy of Cancer cells, providing a novel therapeutic approach for MUC1-positive cancers.

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