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Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax.
MedLine Citation:
PMID:  22570867     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The Bcl-2 family members are key regulators of cellular viability, either promoting or suppressing cell death. Recent reports have indicated that the pro-survival members (Bcl-w, Bcl-XL, and others) also enhance the migratory and invasive potentials of cancer cells, although the mechanisms underlying this phenomenon have yet to be adequately elucidated. Herein, by using human cancer cells and mouse embryonic fibroblasts, we demonstrate that Bcl-w functions in the mitochondria to increase the levels of reactive oxygen species (ROS), which subsequently stimulates the invasion-promoting signaling pathway. By way of contrast, Bax,a member of the multidomain pro-apoptotic group (Bax and Bak), was found to reduce ROS levels, thereby suppressing cell invasion. Analyses of the functional relationship between Bcl-w and Bax have shown that Bcl-w requires Bax for promoting cell invasion, whereas Bax suppresses cell invasion in a Bcl-win dependent manner. By using a Bcl-w mutant (Bcl-w/G94A) that was found not to bind to Bax, we have further determined that Bcl-w should bind to Bax to promote cell invasion. Overall, the results indicate that Bcl-w enhances cellular invasiveness by binding to Bax and subsequently blocking its invasion suppressing actions. Moreover, these functions of Bcl-w and Bax are mimicked by other pro-survival and pro-apoptotic members, such as Bcl-XL and Bak, respectively. We propose the balance between prosurvival and multidomain pro-apoptotic members as a novel determinant of cellular invasiveness.
Authors:
Eun Mi Kim; Jongdoo Kim; Jong Kuk Park; Sang-Gu Hwang; Wun-Jae Kim; Won-Jae Lee; Sang Won Kang; Hong-Duck Um
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular signalling     Volume:  24     ISSN:  1873-3913     ISO Abbreviation:  Cell. Signal.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  1163-72     Citation Subset:  IM    
Affiliation:
Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
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