Back to Search
Start Over
Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis.
- Source :
- Molecular Cancer; 10/11/2024, Vol. 23 Issue 1, p1-20, 20p
- Publication Year :
- 2024
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14764598
- Volume :
- 23
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Molecular Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 180213784
- Full Text :
- https://doi.org/10.1186/s12943-024-02138-0