title: G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways.
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.
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Colorectal and Anal Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yao
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000367:Age Factors; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D013274:Stomach Neoplasms / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C554061:GNAQ protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D043802:GTP-Binding Protein alpha Subunits, Gq-G11