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SPP1 promotes ovarian cancer progression via Integrin β1/FAK/Akt signaling pathway

Authors Zeng B, Zhou M, Wu H, Xiong Z

Received 16 October 2017

Accepted for publication 16 December 2017

Published 12 March 2018 Volume 2018:11 Pages 1333—1343

DOI https://doi.org/10.2147/OTT.S154215

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 4

Editor who approved publication: Dr Ingrid Espinoza


Biao Zeng, Min Zhou, Huan Wu, Zhengai Xiong

Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China


Objectives: Ovarian cancer is one of the most lethal malignant tumors in women. Secreted phosphoprotein 1 (SPP1) plays an important role in some cancer types. Therefore, the role of SPP1 in ovarian cancer was determined and the potential mechanism was elucidated.
Materials and methods: The expression of SPP1 in ovarian cancer was determined by immunohistochemistry in ovarian cancer tissues and normal ovarian tissues. Cellular proliferation, migration, and invasion were determined by cell counting kit-8 assay, wound healing assay, and Matrigel invasion assay in SKOV3 and A2780 cells. The protein expression of SPP1, integrin subunit β1 (Integrin β1), focal adhesion kinase (FAK), and phosphorylation protein kinase B (p-AKT) was detected by Western blotting in SKOV3 cells after silencing SPP1. The expression of SPP1 was determined in SKOV3 cells after transfecting with miR-181a mimics or inhibitors. The growth of SKOV3 cells in vivo was determined in a nude mouse model of ovarian cancer after silencing SPP1.
Results: The expression of SPP1 was higher in epithelial ovarian cancer tissues than in normal ovarian tissues. Silencing SPP1 decreased the cell proliferation, migration, and invasion. Ectopic expression of SPP1 increased the cell proliferation, migration, and invasion. Silencing SPP1 prevented ovarian cancer growth in mice. Silencing SPP1 inhibited Integrin β1/FAK/AKT pathway. In agreement, ectopically expressed SPP1 activated Integrin β1/FAK/AKT pathway. Also, SPP1 was regulated by miR-181a.
Conclusion: SPP1 is a biomarker for the prognosis of ovarian cancer. It is also oncogenic and a potential target for ovarian cancer therapy.

Keywords: ovarian cancer, SPP1, Integrin β1, FAK, AKT, miR-181a

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