Effect of hypoxia-regulated CD151 expression on cancer cell adhesion

• Main Authors: Chun-wei Chien, 簡郡緯
• Other Authors: Shaw-Jeng Tsai
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/74305384767918324161

碩士 === 國立成功大學 === 生理學研究所 === 95 === CD151 is a member of tetraspanin family that plays important roles in cell adhesion and motility. However, the regulation of CD151 expression in normal and cancerous cells has not yet revealed. In cancer tissue, it is suggested that CD151 acts as a metastasis-suppressor while hypoxia has been shown to be a factor of causing metastasis. We hypothesize that hypoxia-induced cancer cell metastasis may be mediated via deregulation of CD151. Indeed, colon cancer cells expressed less CD151 than its normal counterpart, which is inversely correlated with the expression of hypoxia-inducible factor-1�� (HIF-1��). By using bioinformatic approach, we identified a putative hypoxia response element (HRE) in the promoter region of human CD151 gene. Treatment of colon cancer cells with hypoxia or chemicals that are known to increase accumulation of HIF-1�� resulted in decreased CD151 expression. Promoter activity assay further demonstrated that the predicted putative HRE was pivotal for HIF-1��-dependent downregulation of CD151 expression. Furthermore, inhibition of CD151 expression by hypoxia resulted in decreased cancer cell adhesion to laminin-coated matrix, a process that enables cancer cell to detach from its surrounding matrix and be ready for metastasis. In conclusion, we demonstrated that hypoxia downregulates the expression of CD151 thus enhances the detachment of cancer cells from its basement membrane protein, an important first step for metastasis.