Platelet derived TGF-β promotes cervical carcinoma cell growth by suppressing KLF6 expression
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Ao-Di He1,*, Shao-Ping Wang2,*, Wen Xie1, Wei Song1, Shuo Miao1, Ru-Ping Yang1, Ying Zhu1, Ji-Zhou Xiang1 and Zhang-Yin Ming1,3
1Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science & Technology, Wuhan 430030, China
2Department of Hepatobiliary Surgery, Affiliated Futian Hospital of Guangdong Medical College, Shenzhen 518033, China
3The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China
*These authors have contributed equally to this work and are designated as co-first authors
Zhang-Yin Ming, email: [email protected]
Keywords: platelet, platelet releasate, HeLa cervical carcinoma cells, Krüppel-like factor 6, transforming growth factor beta
Abbreviations: CRP, collagen-related peptide; KLF6, Krüppel-like factor 6; MTT, 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide; siRNA, small interfering RNA; TGF-β, transforming growth factor beta
Received: April 25, 2017 Accepted: July 12, 2017 Published: August 03, 2017
Platelets in the primary tumor microenvironment play crucial roles in regulating tumor growth, metastasis, and angiogenesis, but the underlying mechanisms are unclear. Here, we show that platelet releasates exhibited a proliferative effect on HeLa cells, and this effect correlated with a reduction of KLF6 expression. After incubation with either washed human platelets or collagen-related peptide (CRP) activated platelet releasates, expression of KLF6 in the HeLa cervical tumor cell line was markedly reduced. However, no significant difference was observed between control HeLa cells and HeLa cells incubated with resuspended activated platelet pellet. Moreover, the platelets’ promoting effect on HeLa cell growth was significantly abolished in KLF6 silenced HeLa cells. In addition, blocking TGF-β signaling with SB431542, a TGF-β receptor inhibitor, also counteracted the effect of platelets on proliferation and KLF6 expression in HeLa cells. From these findings, we conclude that platelet derived TGF-β promotes proliferation of HeLa cells by decreasing the expression of KLF6. The discovery that KLF6 is a key target of platelet-derived TGF-β signaling in HeLa cells identifies a potential new therapeutic target for the prevention and treatment of cervical carcinoma.
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