Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy.

Autophagy ·第 11 卷 ·第 5 期 ·2016-02-23

Shi Yin, Tan Shi-Hao, Ng Shukie, Zhou Jing, Yang Na-Di, Koo Gi-Bang, McMahon Kerrie-Ann, Parton Robert G, Hill Michelle M, Del Pozo Miguel A, Kim You-Sun, Shen Han-Ming

摘要

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.

关键词

ATP6V0D1 ATPase H+ transporting lysosomal 38kDa V0 subunit d1 Baf bafilomycin A1 CAV1 caveolin 1 CHO water-soluble cholesterol CQ choloroquine CTSL cathepsin L CTxB cholera toxin subunit B DRF detergent-resistant fraction DSF detergent-soluble fraction EGF epidermal growth factor KO knockout LAMP1 lysosomal-associated membrane protein 1 MAP1LC3/LC3 microtubule-associated protein 1 light chain 3 MBCD methyl-β-cyclodextrin MEF mouse embryonic fibroblasts MTOR mechanistic target of rapamycin PBS phosphate-buffered saline PI propidium iodide PLA proximity ligation assay PTRF polymerase I and transcript release factor TFRC transferrin receptor TSC tuberous sclerosis complex WT wild type. autophagy breast cancer caveolin 1 lipid rafts lysosome tfLC3B mRFP-GFP tandem fluorescent-tagged LC3B

文献信息

期刊

Autophagy

期刊简称

Autophagy

ISSN

1554-8627

发表日期

2016-02-23

收录日期

2015-05-29

更新日期

2016-05-06

语言

英语

国家/地区

United States

NLM ID

101265188

外部链接

PubMed 原文查看期刊详情

分析服务

Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy.

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