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Cell Death & Disease

Cell Death & Disease

IF: 8.1
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The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization

Published:26 October 2022 DOI: 10.1038/s41419-022-05345-z PMID: 36289190
Quanfu Li, Yunkai Chu, Shengze Li, Liping Yu, Huayun Deng, Chunhua Liao, Xiaodong Liao, Chihyu Yang, Min Qi, Jinke Cheng, Guoqiang Chen, Lei Huang

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.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Bortezomib 179324-69-7 C19H25BN4O4 873 suppliers $10.00-$2516.45
Bortezomib 179324-69-7 C19H25BN4O4 873 suppliers $10.00-$2516.45
Bortezomib 179324-69-7 C19H25BN4O4 873 suppliers $10.00-$2516.45
Bortezomib 179324-69-7 C19H25BN4O4 873 suppliers $10.00-$2516.45
MG-132 133407-82-6 C26H41N3O5 428 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 428 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 428 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 428 suppliers $11.00-$9807.90
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone 338967-87-6 C15H10Cl2N2O2S 212 suppliers $12.00-$1200.00
3-(2,4-Dichloro-5-methoxyphenyl)-2,3-dihydro-2-thioxo-4(1H)-quinazolinone 338967-87-6 C15H10Cl2N2O2S 212 suppliers $12.00-$1200.00

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