Metastasis Suppressor KAI1/CD82 Attenuates the Matrix Adhesion of Human Prostate Cancer Cells by Suppressing Fibronectin Expression and β1 Integrin Activation
Metastasis Suppressor KAI1/CD82 Attenuates the Matrix Adhesion of Human Prostate Cancer Cells by Suppressing Fibronectin Expression and β1 Integrin Activation
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DOI：
10.1159/000329979
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Lee, Hansoo
中科院分区：
文献类型：
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作者：
Lee, Hyun-Ah;Park, Iha;Lee, Hansoo
KAI1/CD82 是一种四跨膜蛋白，在多种人类癌症中充当转移抑制剂，并已被证明可以调节细胞粘附特性。在本研究中，我们利用人前列腺癌细胞研究了 KAI1/CD82 介导的细胞粘附与细胞外基质变化的潜在机制。我们发现高 KAI1/CD82 表达减弱了细胞对未包被或纤连蛋白包被板的短期粘附。此外，与低KAI1/CD82表达相比，高KAI1/CD82表达产生了不利于细胞粘附的细胞外环境，这表明细胞外基质（ECM）分子表达和/或分泌的KAI1/CD82依赖性调节。在检查的 ECM 成分中，纤连蛋白在高 KAI1/CD82 表达细胞中表现出表达和分泌减少。此外，高KAI1/CD82表达干扰了细胞表面β(1)整合素的激活，而总β(1)整合素水平保持不变，同时减少了粘着斑复合物的形成和肌动蛋白丝的成束减少。最后，在划伤实验中，高 KAI1/CD82 表达显着阻碍了细胞运动。综上所述，我们的结果强烈表明，KAI1/CD82 减弱 β(1) 整合素的激活，从而下调 β(1) 整合素的由外向内信号传导，导致粘着斑形成和纤连蛋白表达/分泌减少，从而干扰细胞粘附特性和运动。版权所有 (C) 2011 S. Karger AG，巴塞尔
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 beta(1) integrin at the cell surface while total beta(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 beta(1) integrin, and thereby down-regulates outside-in signaling of beta(1) integrin, leading to the reduction of focal adhesion formation and fibronectin expression/secretion, which subsequently interferes with cell adhesion properties and motility. Copyright (C) 2011 S. Karger AG, Basel