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Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells |
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| Authors: | Xiangxuan Zhao Yong Liu Qi Ma Xiaohui Wang Maryam Mehrpour Quan Chen |
| Institution: | a The Joint Laboratory of Apoptosis and Cancer Biology, The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China b The Graduate University of Chinese Academy of Sciences, Beijing 100049, China c College of Life Science, Nankai University, Tianjin 300071, China d INSERM U756, Faculté de pharmacie; Université Paris-Sud F-92296 Chatenay Malabry, France |
| Abstract: | The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) offers promising therapeutic potential based on its ability to induce apoptosis in various cancer cell lines without obvious adverse effect to normal cells. However, the mechanism of the differential sensitivity towards TRAIL-induced apoptosis remains unclear. Here, we demonstrate that caveolin-1 directly regulated TRAIL-induced apoptosis in HepG2 cells. ShRNA-mediated caveolin knockdown sensitized TRAIL-induced apoptosis and disruption of caveolae structure by the cholesterol-extracting reagent, methyl-β-cyclodextrin (MCD), enhanced TRAIL-induced apoptosis. Over-expression of caveolin-1 partially blocked TRAIL-induced apoptosis. The engagement of TRAIL with its receptor DR4 reduced the localization of DR4 in caveolae and resulted in its internalization. Blockade of caveolae-mediated internalization of DR4 by filipin III effectively enhanced TRAIL-induced apoptosis. Collectively, our results reveal a new mechanism by which caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells. |
| Keywords: | Caveolin-1/Caveolae Apoptosis TRAIL Death receptor-4 |
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