Metastasis Suppressor KAI1/CD82 Attenuates the Matrix Adhesion of Human Prostate Cancer Cells by Suppressing Fibronectin Expression and β 1 Integrin Activation

Cellular Physiology and Biochemistry

关键词: Fibronectin;    KAI1;    CD82;    Metastasis;    Adhesion;    Integrin;    Extracellular matrix;   

DOI  :  10.1159/000329979

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

KAI1/CD82, a tetraspanin membrane protein functions as a metastasis suppressor in many types of human cancers and has been shown to regulate cell adhesion properties. In the present study, we investigated the underlying mechanism of KAI1/CD82-mediated changes in cell adhesion to the extracellular matrix using human prostate cancer cells. We found that high KAI1/CD82 expression attenuated short-term cell adhesion to uncoated- or fibronectin-coated plates. Moreover, high KAI1/CD82 expression generated an extracellular environment unfavorable for cell adhesion as compared to low KAI1/CD82 expression, suggesting KAI1/CD82-dependent regulation of extracellular matrix (ECM) molecule(s) expression and/or secretion. Among ECM components examined, fibronectin exhibited decreased expression and secretion in high KAI1/CD82-expressing cells. Furthermore, high KAI1/CD82 expression interfered with the activation of β ₁ integrin at the cell surface while total β ₁ integrin levels remained unchanged, concomitant with reduced formation of focal adhesion complex and decreased bundling of actin filaments. Finally, high KAI1/CD82 expression significantly retarded cell motility in a scratch wound assay. Taken together, our results strongly suggest that KAI1/CD82 attenuates the activation of β ₁ integrin, and thereby down-regulates outside-in signaling of β ₁ integrin, leading to the reduction of focal adhesion formation and fibronectin expression/secretion, which subsequently interferes with cell adhesion properties and motility.

【 授权许可】

CC BY-NC-ND