Numerous types of cancer cells migrate into extracellular tissues. This phenomenon is termed invasion, and is associated with poor prognosis in cancer patients. In this study, we demonstrated that filamin B (FLNb), an actin-binding protein, is highly expressed in cancer cell lines that exhibit high invasiveness, with a spindle morphology, into 3D collagen matrices. In addition, we determined that knockdown of FLNb in invasive cancer cells converts cell morphology from spindle-shaped, which is associated with high invasiveness, to round-shaped with low invasiveness. Furthermore, di-phosphorylation of myosin regulatory light chain (MRLC) and phosphorylation of focal adhesion kinase (FAK) are inhibited in FLNb-knockdown cancer cells. These results suggest that FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK. Therefore, FLNb may be a new therapeutic target for invasive cancers.
The actin-cytoskeleton plays a critical role in various biological processes, including cell migration, development, tissue remodeling, and memory formation. Both extracellular and intracellular signals regulate reorganization of the actin-cytoskeleton to modulate tissue architecture and cellular morphology in a spatiotemporal manner. Since the discovery that activation of Rho family GTPases induces actin-cytoskeleton reorganization, the mode of action of Rho family GTPases has been extensively studied and individual effectors have been characterized. The actin-binding protein IQGAP1 was identified as an effector of Rac and Cdc42 and is the founding member of the IQGAP family with two additional isoforms. The IQGAP family shows conserved domain organization, and each member displays a specific expression pattern in mammalian tissues. IQGAPs regulate the actin-cytoskeleton alone and with their binding partners, thereby controlling diverse cellular processes, such as cell migration and adhesion. Here, we introduce IQGAPs as an actin-cytoskeleton regulator.
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