Involvement of caveolin-1 in low shear stress-induced breast cancer cell motility and adhesion: Roles of FAK/Src and ROCK/p-MLC pathways.
Tumor cells translocating to distant sites are subjected to hemodynamic shear forces during their passage in the blood vessels. Low shear stress (LSS) plays a critical role in the regulation of various aspects of tumor cells functions, including motility and adhesion. Beyond its structural role, caveolin-1 (Cav-1), the important component of caveolae, represents a modulator of several cancer-associated functions as tumor progression and metastasis. However, the role of Cav-1 in regulating tumor cells response to shear stress remains poorly explored. Here, we characterized the role of LSS and Cav-1 in mediating cell motility and adhesion on human breast carcinoma MDA-MB-231 cells. We first showed that LSS exposure promoted cell polarity and focal adhesion (FA) dynamics, thus indicating elevated cell migration. Silencing of Cav-1 leaded to a significantly lower formation of stress fibers. However, LSS exposure was able to rescue it via the alteration of actin-associated proteins expression, including ROCK, p-MLC, cofilin and filamin A. Time-lapse migration assay indicated that Cav-1 expression fostered MDA-MB-231 cells motility and LSS triggered cells to rapidly generate new lamellipodia. Furthermore, Cav-1 and LSS significantly influenced cell adhesion. Taken together, our findings provide insights into mechanisms underlying LSS triggered events mediated by downstream Cav-1, including FAK/Src and ROCK/p-MLC pathways, involved in the reorganization of the cytoskeleton, cell motility, FA dynamics and breast cancer cell adhesion.
['Xiong|Niya|N|', 'Li|Shun|S|', 'Tang|Kai|K|', 'Bai|Hongxia|H|', 'Peng|Yueting|Y|', 'Yang|Hong|H|', 'Wu|Chunhui|C|', 'Liu|Yiyao|Y|']
D008841:Actin Cytoskeleton D001696:Biomechanical Phenomena D051242:Caveolin 1 D002448:Cell Adhesion D045744:Cell Line, Tumor D002465:Cell Movement D051338:Cofilin 1 D004847:Epithelial Cells D064448:Filamins D051417:Focal Adhesion Kinase 1 D022001:Focal Adhesions D015972:Gene Expression Regulation, Neoplastic D006801:Humans D042361:Mammary Glands, Human D008565:Membrane Proteins D011554:Pseudopodia D034741:RNA, Small Interfering D015398:Signal Transduction D013314:Stress, Mechanical D054460:rho-Associated Kinases D019061:src-Family Kinases
Caveolin-1 Cell motility ROCK Low shear stress Focal adhesion MLC