Abstract
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.
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Abbreviations
- BCL2 :
-
(human gene)
- Bcl2 :
-
(mouse gene)
- BCL2:
-
(human and mouse protein)
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Acknowledgements
We thank Dr Jau-shyong Hong (NIEHS), Dr Bob Petrovich (NIEHS), Ms Pamela D Arora (CIHR, Toronto), and Dr Yanhong Liao (Huazhong University) for materials, Dr Jeff Chou (NIEHS) for statistics, and Dr James Williams (NIEHS) for mass spectra analysis. We also thank Dr Azad Bonni (Harvard Medical School) for providing plasmid-expressing GST-bad. The Division of Intramural Research of the NIEHS, NIH supported this research through projects Z01-ES02302511 and Z01-ES2120714.
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Supplementary information
Supplementary information, Figure S1
Over expression of Bcl–2 in B6 Melanoma cells also significantly decreased cell motility. (PDF 79 kb)
Supplementary information, Figure S2
Recombinant human BCL2 protein slightly increased actin polymerization. (PDF 75 kb)
Supplementary information, Figure S3
Overexpression of BCL2 inhibited 12G10 antibody induced cell–cell adhesions in MCF–7 cells resembling the effect of Jasplakinolide. (PDF 128 kb)
Supplementary information, Data S1
Materials and Methods (PDF 118 kb)
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Ke, H., Parron, V., Reece, J. et al. BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization. Cell Res 20, 458–469 (2010). https://doi.org/10.1038/cr.2010.21
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DOI: https://doi.org/10.1038/cr.2010.21
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