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유기준Ki-jun Ryu

경상국립대학교

Mol. Cancer, Oct 11 2024, 23 (1) 227 | https://doi.org/10.1186/s12943-024-02138-0 Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis

Ki-Jun Ryu ^1,†, Ki Won Lee ^1,†, Seung-Ho Park ², Taeyoung Kim ¹, Keun-Seok Hong ¹, Hyemin Kim¹, Minju Kim ¹, Dong Woo Ok ¹, Gu Neut Bom Kwon ¹, Young-Jun Park ², Hyuk-Kwon Kwon^1,3, Cheol Hwangbo ^1,3, Kwang Dong Kim ^1,3, J. Eugene Lee ⁴ and Jiyun Yoo ^1,3,*

¹Division of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, Korea
²Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea
³Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea
⁴Division of Biometrology, Korea Research Institute of Standards and Science, Daejeon 34113, Korea

^*Corresponding author: correspondence to Jiyun Yoo

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.

논문정보

형식Research article
게재일2024년 10월 (BRIC 등록일 2024-10-16)
연구진국내 연구진
분야 생명과학 > 세포생물학

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