A localization gate licenses chaperone-mediated autophagy of SNAI (snail) to restrain epithelial-mesenchymal transition competence in breast cancer - PubMed
2 months ago
- #Autophagy
- #Metastasis
- #Breast Cancer
- SNAI(蜗牛蛋白)是乳腺癌上皮-间质转化(EMT)的关键调控因子
- SNAI被鉴定为分子伴侣介导的自噬(CMA)底物,其降解受核质转运调控
- 敲除CMA组分(HSPA8/HSC70或LAMP2A)会升高SNAI水平并延长其半衰期
- CMA抗性SNAI突变体能增强EMT效应,包括迁移、侵袭和转移能力
- 在三阴性乳腺癌中,SNAI主要定位于细胞核,使其在正常情况下无法被CMA降解
- 血清饥饿可促进SNAI核输出,从而启动CMA依赖性降解,该过程可被瘦素霉素B阻断
- 研究表明增强CMA活性或促进SNAI胞质暴露可抑制EMT驱动的癌症进展