Department of Dermatology, Duke University Medical Center, Durham, NC, USA.
Cell Adh Migr. 2011 Jan-Feb;5(1):6-10. doi: 10.4161/cam.5.1.13175. Epub 2011 Jan 1.
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.
除了在细胞凋亡中作为拮抗剂的明确作用外，我们还提出，BCL2 在某些条件下可能作为细胞运动和黏附的细胞内抑制剂。我们的证据表明，BCL2 在癌细胞和非癌细胞中过度表达时，可以与肌动蛋白和凝胶蛋白形成复合物，该复合物通过降低凝胶蛋白的切割活性来增加肌动蛋白聚合，从而抑制细胞黏附过程。一方面，BCL2 的增加与肌动蛋白聚合的增加，以及细胞黏附、扩散和运动的抑制之间存在联系，这是一个新的观察结果，可能为为什么某些肿瘤中 BCL2 的过度表达与患者生存改善相关提供了合理的解释。此外，我们已经在体外确定了可以增加 F-肌动蛋白聚合而减少细胞运动的条件。这些发现强调了 BCL2 可能参与调节细胞骨架重组的可能性，并为探索对细胞黏附和迁移重要的信号转导途径以及开发用于抑制癌症转移的小分子疗法提供了机会。
