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Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvβ6 integrin-mediated signaling in ovarian cancer

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Abstract

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. αvβ6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to αvβ6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in αvβ6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced αvβ6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by αvβ6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-αvβ6 integrin antibody, respectively. In addition, αvβ6 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 αvβ6 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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Acknowledgments

Financial support was provided by National Natural Science Foundation of China (NSFC) (No. 30872740).

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The authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Baoyao Xue, Kan Huang, Tingting Xie, Xiaobo Xu, Hongju Zhang, Chunlei Qi, Junli Ge & Yuecheng Yu

  2. Department of Obstetrics and Gynecology, Affiliated Hospital of Armed Police Logistics College, Tianjin, 300162, China

    Weiguang Wu

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  1. Baoyao Xue
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  2. Weiguang Wu
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  3. Kan Huang
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  4. Tingting Xie
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  5. Xiaobo Xu
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  6. Hongju Zhang
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  7. Chunlei Qi
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  9. Yuecheng Yu
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Correspondence to Yuecheng Yu.

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Baoyao Xue, Weiguang Wu, and Kan Huang contributed equally to this work.

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Xue, B., Wu, W., Huang, K. et al. Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvβ6 integrin-mediated signaling in ovarian cancer. Mol Cell Biochem 380, 177–184 (2013). https://doi.org/10.1007/s11010-013-1671-1

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  • DOI: https://doi.org/10.1007/s11010-013-1671-1

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