The receptor for activated protein kinase C promotes cell growth, invasion and migration in cervical cancer

Liao,Shan; Xiao,Songshu; Chen,Hongxiang; Zhang,Manying; Chen,Zhifang; Long,Yuehua; Gao,Lu; He,Junyu; Ge,Yanshan; Yi,Wei; Wu,Minghua; Li,Guiyuan; Zhou,Yanhong

doi:10.3892/ijo.2017.4137

The receptor for activated protein kinase C promotes cell growth, invasion and migration in cervical cancer

Authors:
- Shan Liao
- Songshu Xiao
- Hongxiang Chen
- Manying Zhang
- Zhifang Chen
- Yuehua Long
- Lu Gao
- Junyu He
- Yanshan Ge
- Wei Yi
- Minghua Wu
- Guiyuan Li
- Yanhong Zhou
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Affiliations: Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, P.R. China, Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China, The Gynecology Department, People's Hospital of Xinjiang, Urumchi, Xinjiang, P.R. China, The Gynecology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumchi, Xinjiang, P.R. China
Published online on: September 27, 2017 https://doi.org/10.3892/ijo.2017.4137
Pages: 1497-1507
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cervical cancer is one of the most common malignant tumors in women all over the world. However, the exact etiology of cervical cancer remains unclear. The receptor for activated protein kinase C (RACK1) is reported to be involved in tumorigenesis and tumor progression. Besides, the prognostic value of RACK1 in several kinds of tumors has been identified. However, there are limited studies on the functional role of RACK1 in cervical cancer. In this study, we tested the expression level of RACK1 by immunohistochemistry and western blot technologies and find that it is upregulated in cervical cancer. Colony formation and CCK8 assays indicate that RACK1 promotes cell proliferation in CaSki cervical cancer cells. While the silence of RACK1 decreases the cell proliferation in CCK8 analysis. β-galactosidase staining suggests that RACK1 decreases cell senescence in cervical cancer cells. Invasion and migration assay show that RACK1 promotes the invasion and migration of cervical cancer cells. Also, when RACK1 was silenced, it exerts the opposite result. Furthermore, the mRNA expression levels of MMP‑3, MMP‑9 and MMP‑10 were upregulated in RACK1‑overexpressed CaSki cells by qPCR analysis. RACK1 also induces S phase accumulation in cell cycle analysis and suppresses cell apoptosis in cervical cancer cells. Flow cytometry analysis of mitochondria functions suggests that RACK1 increases the mitochondrial membrane potential (Δψm) levels to prevent mitochondrial apoptosis in cervical cancer cells. To explore the possible mechanism of RACK1, we tested and found that RACK1 upregulates the expression of NF-κB, cyclin D1 and CDK4 and downregulates the expression of p53, p38, p21 and STAT1 in cervical cancer cells. These results suggest that RACK1 promotes cell growth and invasion and inhibits the senescence and apoptosis in cervical cancer cells probably by affecting the p53 pathway.

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