Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer

Zhao,Jing; Ye,Wei; Wu,Juan; Liu,Lijuan; Yang,Lina; Gao,Lu; Chen,Biliang; Zhang,Fanglin; Yang,Hong; Li,Yu

doi:10.3892/or.2015.3999

Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer

Authors:
- Jing Zhao
- Wei Ye
- Juan Wu
- Lijuan Liu
- Lina Yang
- Lu Gao
- Biliang Chen
- Fanglin Zhang
- Hong Yang
- Yu Li
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Affiliations: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Microbiology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: May 20, 2015 https://doi.org/10.3892/or.2015.3999
Pages: 67-76

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Abstract

CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.

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