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Cholesterol depletion induces anoikis-like apoptosis via FAK down-regulation and caveolae internalization

Cited 49 time in Web of Science Cited 52 time in Scopus
Authors
Park, Eun-Kyung; Park, Mi Jung; Lee, Seong-Hee; Li, Ying Chun; Lee, Jae-Seon; Ye, Sang-Kyu; Kim, Chul-Woo; Kim, Yong-Nyun; Park, Byung-Kiu; Park, Jong-Wan; Lee, Jung Weon; Kim, Jungeun
Issue Date
2009-07
Publisher
JOHN WILEY & SONS LTD
Citation
JOURNAL OF PATHOLOGY; Vol.218 3; 337-349
Keywords
lipid rafts/caveolaeanoikischolesterolFAKSrcadhesioncaveolin-1
Abstract
Caveolae (lipid rafts), microdomains of the plasma membrane, are known to contain various signalling molecules and consequently are involved in the regulation of many biological functions. To investigate the role of the caveolae in cell survival and adhesion, we disrupted the caveolae by depletion of cholesterol, a major lipid component of the caveolae, with methyl-beta cyclodextrin (M beta CD) treatment of A431 cells. We found that cholesterol depletion induced an anoikis-like cell death involving actin reorganization, resulting in a decrease in cell spreading and an increase in cell detachment, which was reversed by cholesterol addition. Disruption of caveolae led to the down-regulation of FAK, Src activation, tyrosine phosphorylation of caveolin-1 and mobilization of caveolae markers, GM1 and caveolin-1, from the cell surface to the cytoplasm, which were also recovered by cholesterol addition. The expression of dominant-active FAK was able to delay caveolae internalization and apoptosis and attenuated Akt inactivation by M beta CD, whereas dominant-negative FAK expression resulted in enhanced apoptosis. Moreover, FAK down-regulation by si-RNA resulted in Akt inactivation and thus increased cell death by M beta CD treatment. Our results suggest that the cholesterol content and/or surface levels of the caveolae affect the activity of FAK, which in turn regulates caveolae internalization and cell survival. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN
0022-3417
Language
English
URI
http://hdl.handle.net/10371/76636
DOI
https://doi.org/10.1002/path.2531
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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