Chaperone-mediated Autophagy Modulates Snail Protein Stability: Implications for Breast Cancer Metastasis

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2024 Oct 10

PMID 39390584

Authors

Ki-Jun Ryu

Ki Won Lee

Seung-Ho Park

TaeYoung Kim

Keun-Seok Hong

Hyemin Kim

Minju Kim

Dong Woo Ok

Gu Neut Bom Kwon

Young-Jun Park

Hyuk-Kwon Kwon

Cheol Hwangbo

Kwang Dong Kim

J Eugene Lee

Jiyun Yoo

Affiliations

Soon will be listed here.

Abstract

Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.

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