Site-Specific S-Nitrosylation of Integrin 伪6 Increases the Extent of Prostate Cancer Cell Migration by Enhancing Integrin 尾1 Association and Weakening Adherence to Laminin-1

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• 作者：Jared Isaac ; Pheruza Tarapore ; Xiang Zhang ; Ying-Wai Lam ; Shuk-Mei Ho
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：December 4, 2012
• 年：2012
• 卷：51
• 期：48
• 页码：9689-9697
• 全文大小：435K
• 年卷期：v.51,no.48(December 4, 2012)
• ISSN：1520-4995

文摘

The increased mortality in prostate cancer is usually the result of metastatic progression of the disease from the organ-confined location. Among the major events in this progression cascade are enhanced cell migration and loss of adhesion. Moreover, elevated levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) found within the tumor microenvironment are hallmarks of progression of this cancer. To understand the role of nitrosative stress in prostate cancer progression, we investigated the effects of NO and iNOS on prostate cancer cell migration and adhesion. Our results indicate that ectopic expression of iNOS in prostate cancer cells increased the extent of cell migration, which could be blocked by selective ITG伪6 blocking antibody or iNOS inhibitors. Furthermore, iNOS was found to cause S-nitrosylation of ITG伪6 at Cys86 in prostate cancer cells. By comparing the activities of wild-type ITG伪6 and a Cys86 mutant, we showed that treatment of prostate cancer cells with NO increased the level of ITG伪6 heterodimerization with ITG尾1 but not with ITG尾4. Finally, S-nitrosylation of ITG伪6 weakened its binding to laminin-尾1 and weakened the adhesion of prostate cancer cells to laminin-1. In conclusion, S-nitrosylation of ITG伪6 increased the extent of prostate cancer cell migration, which could be a potential mechanism of NO- and iNOS-induced enhancement of prostate cancer metastasis.