期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 380, 期 1-2, 页码 177-184出版社
SPRINGER
DOI: 10.1007/s11010-013-1671-1
关键词
SDF-1; CXCR4; alpha v beta 6 integrin; Ovarian cancer; Invasion
类别
资金
- National Natural Science Foundation of China (NSFC) [30872740]
Ovarian carcinoma is a common gynecological malignancy and a great threat to health as a result of metastasis. The chemokine stromal-derived factor (SDF-1) plays multiple roles in tumor pathogenesis. However, the precise molecular mechanism underlying SDF-1-induced ovarian cancer cell invasion is still undefined. alpha v beta 6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to alpha v beta 6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in alpha v beta 6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced alpha v beta 6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by alpha v beta 6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-alpha v beta 6 integrin antibody, respectively. In addition, alpha v beta 6 integrin induced the phosphorylation of p38 MAPK and PI3 K/Akt, contributing to the up-regulation of uPA, as treatment with the specific inhibitor for p38 mitogen-activated protein kinases (MAPK) (SB203580) or phosphatidylinositol 3-kinase (PI3 K)/Akt (LY294002) strikingly abrogated uPA expression. Taken together, these results demonstrated that SDF-1 enhanced ovarian cancer cell invasion through alpha v beta 6 integrin-mediated uPA expression via the p38 MAPK and PI3 K/Akt pathway. Consequently, our findings will provide a new explanation about how SDF-1 aggravates the pathogenesis of ovarian cancer.
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