Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax

Eun Mi Kim, Jongdoo Kim, Jong Kuk Park, Sang Gu Hwang, Wun Jae Kim, Won Jae Lee, Sang Won Kang, Hong Duck Um

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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-X L, 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-w-independent 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-X L and Bak, respectively. We propose the balance between pro-survival and multidomain pro-apoptotic members as a novel determinant of cellular invasiveness.

Original languageEnglish
Pages (from-to)1163-1172
Number of pages10
JournalCellular Signalling
Issue number6
StatePublished - Jun 2012

Bibliographical note

Funding Information:
This work was supported by Nuclear Research & Development Program of the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST), and in part by Basic Science Research Program through the NRF.


  • Bcl-2 family
  • Cell death
  • Cell invasion


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