title: Involvement of caveolin-1 in low shear stress-induced breast cancer cell motility and adhesion: Roles of FAK/Src and ROCK/p-MLC pathways.
abstract: 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.
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Niya
authors: N
authors: Xiong
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Shun
authors: S
authors: Li
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Kai
authors: K
authors: Tang
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Hongxia
authors: H
authors: Bai
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Yueting
authors: Y
authors: Peng
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Hong
authors: H
authors: Yang
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
authors: Chunhui
authors: C
authors: Wu
authors: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China. Electronic address: liuyiyao@uestc.edu.cn.
authors: Yiyao
authors: Y
authors: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D001696:Biomechanical Phenomena; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D064448:Filamins / Q000235:genetics / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; C495810:CFL1 protein, human; D051242:Caveolin 1; D051338:Cofilin 1; D064448:Filamins; C425069:MLC1 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases
keywords: Caveolin-1; Cell motility; Focal adhesion; Low shear stress; MLC; ROCK