BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization.
BCL2 is best known as a multifunctional anti-apoptotic protein. However, little is known about its role in cell-adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, the loss of Bcl2 resulted in higher motility observed in Bcl2-null mouse embryonic fibroblast (MEF) cells compared to wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin, and gelsolin, which appears to functionally decrease the severing activity of gelsolin. We have observed that the lysate from MCF-7 and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin complexes (which possibly contain other proteins) appears to play a critical role in the regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why the expression of BCL2 in some tumor cell types reduces the potential for metastasis and is associated with improved patient prognosis.
Ke
Hengning
H
Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. hk71@notes.duke.edu
Parron
Vandy I
VI
Reece
Jeff
J
Zhang
Jennifer Y
JY
Akiyama
Steven K
SK
French
John E
JE
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018260:Gelsolin / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D018260:Gelsolin; D019253:Proto-Oncogene Proteins c-bcl-2