A localization gate licenses chaperone-mediated autophagy of SNAI (snail) to restrain epithelial-mesenchymal transition competence in breast cancer - PubMed
6 hours ago
- #Autophagy
- #Metastasis
- #Breast Cancer
- SNAI (snail) is a key regulator of epithelial-mesenchymal transition (EMT) in breast cancer.
- SNAI is identified as a substrate of chaperone-mediated autophagy (CMA), with its degradation controlled by nucleocytoplasmic trafficking.
- Depletion of CMA components (HSPA8/HSC70 or LAMP2A) increases SNAI levels and extends its half-life.
- A CMA-resistant SNAI mutant enhances EMT outputs, including migration, invasion, and metastasis.
- In triple-negative breast cancer, SNAI is predominantly nuclear, making it inaccessible to CMA under normal conditions.
- Serum starvation promotes SNAI nuclear export, enabling CMA-dependent degradation, which can be blocked by leptomycin B.
- The study suggests enhancing CMA or promoting cytosolic exposure of SNAI could attenuate EMT-driven cancer progression.