G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways

Wang,Yizhuo; Xiao,Huijie; Wu,Haitao; Yao,Cheng; He,Hua; Wang,Chang; Li,Wei

doi:10.3892/or.2017.5500

G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways

Authors:
- Yizhuo Wang
- Huijie Xiao
- Haitao Wu
- Cheng Yao
- Hua He
- Chang Wang
- Wei Li
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Affiliations: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Gastrointestinal Colorectal and Anal Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: March 13, 2017 https://doi.org/10.3892/or.2017.5500
Pages: 1998-2006
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Genetic alterations in G protein subunit α q (GNAQ) have been reported in numerous types of human cancer. However, the role of GNAQ in human gastric cancer (GC) has not been explored. In the present study, we found that GNAQ was highly expressed in GC patient samples and GNAQ expression was related to patient age, GC differentiation status and adjuvant therapy, as determined by immunohistochemical assay. Lentivirus delivery of short hairpin RNA (shRNA) targeting GNAQ was used to explore the function of GNAQ in GC cells. Silencing of GNAQ markedly suppressed proliferation and colony formation in GC cells, and arrested the cell cycle at the S phase. Mechanistic analysis revealed that knockdown of GNAQ significantly increased the expression of p53 and p21, and decreased cyclin A and p-CDK2 protein expression. Moreover, the phosphorylation of ERK and MEK was also decreased after knockdown of GNAQ as determined by western blotting assay. Overall, our results suggest that GNAQ plays a critical role in regulating GC cell growth and survival via canonical oncogenic signaling pathways including MAPK and p53, and therefore serves as a promising new therapeutic target in GC.

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