CAV1(小窝蛋白1,小窝蛋白,22kDa)是众所周知的Caveolae的主要支架蛋白,一种特殊的质膜结构.相对而言,对CAV1的caveolae独立功能的研究较少。自噬是一个已知涉及各种膜结构的过程,包括自噬体,溶酶体,和降解细胞内蛋白质和细胞器的自体溶酶体。目前,CAV1在自噬中的功能在很大程度上仍然难以捉摸。在这项研究中,我们首次证明CAV1缺乏促进基础和诱导型自噬。有趣的是,其促进作用主要表现在自噬晚期,通过增强溶酶体功能和自噬-溶酶体融合。值得注意的是,发现CAV1在溶酶体和自噬中的调节功能是不依赖于小窝的,并通过脂筏起作用。此外,CAV1缺乏引起的自噬水平升高是一种饥饿状态下的细胞存活机制。重要的是,在人乳腺癌细胞和组织中观察到CAV1的下调和自噬水平的增强。一起来看,我们的数据揭示了CAV1和脂筏通过调节溶酶体功能和自噬在乳腺癌发展中的新功能。
CAV1 (caveolin 1, caveolae protein, 22kDa) is well known as a principal scaffolding protein of caveolae, a specialized plasma membrane structure. Relatively, the caveolae-independent function of CAV1 is less studied. Autophagy is a process known to involve various membrane structures, including autophagosomes, lysosomes, and autolysosomes for degradation of intracellular proteins and organelles. Currently, the function of CAV1 in autophagy remains largely elusive. In this study, we demonstrate for the first time that CAV1 deficiency promotes both basal and inducible autophagy. Interestingly, the promoting effect was found mainly in the late stage of autophagy via enhancing lysosomal function and autophagosome-lysosome fusion. Notably, the regulatory function of CAV1 in lysosome and autophagy was found to be caveolae-independent, and acts through lipid rafts. Furthermore, the elevated autophagy level induced by CAV1 deficiency serves as a cell survival mechanism under starvation. Importantly, downregulation of CAV1 and enhanced autophagy level were observed in human breast cancer cells and tissues. Taken together, our data reveal a novel function of CAV1 and lipid rafts in breast cancer development via modulation of lysosomal function and autophagy.