title: BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization.
abstract: In addition to its well-defined role as an antagonist in apoptosis, we propose that BCL2 may act as an intracellular suppressor of cell motility and adhesion under certain conditions. Our evidence shows that, when over-expressed in both cancer and non-cancer cells, BCL2 can form a complex with actin and gelsolin that functions to decrease gelsolin-severing activity to increase actin polymerization, and, thus, suppress cell adhesive processes. The linkage between increased BCL2 and increased actin polymerization on the one hand, and suppression of cell adhesion, spreading, and motility on the other hand, is a novel observation that may provide a plausible explanation for why BCL2 over-expression in some tumors is correlated with improved patient survival. In addition, we have identified conditions in vitro in which F-actin polymerization can be increased while cell motility is reduced. These findings underscore the possibility that BCL2 may be involved in modulating cytoskeleton reorganization, and may provide an opportunity to explore signal transduction pathways important for cell adhesion and migration and to develop small molecule therapies for suppression of cancer metastasis.
authors: Department of Dermatology, Duke University Medical Center, Durham, NC, USA.
authors: Hengning
authors: H
authors: Ke
authors: Jennifer Y
authors: JY
authors: Zhang
authors: Steven K
authors: SK
authors: Akiyama
authors: John E
authors: JE
authors: French
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D018260:Gelsolin / Q000378:metabolism; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology; D058105:Polymerization; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000199:Actins; D018260:Gelsolin; D019253:Proto-Oncogene Proteins c-bcl-2