title: GNA13 as a prognostic factor and mediator of gastric cancer progression.
abstract: Guanine nucleotide binding protein (G protein), alpha 13 (GNA13) has been implicated as an oncogenic protein in several human cancers. In this study, GNA13 was characterized for its role in gastric cancer (GC) progression and underlying molecular mechanisms. The expression dynamics of GNA13 were examined by immunohistochemistry (IHC) in two independent cohorts of GC samples. A series of in-vivo and in-vitro assays was performed to elucidate the function of GNA13 in GC and its underlying mechanisms. In both two cohorts of GC samples, we observed that GNA13 was markedly overexpressed in GC tissues and associated closely with aggressive magnitude of GC progression and poor patients' survival. Further study showed that upregulation of GNA13 expression increased the proliferation and tumorigenicity of GC cells in vitro and in vivo, by promoting cell growth rate, colony formation, and tumor formation in nude mice. By contrast, knockdown of GNA13 effectively suppressed the proliferation and tumorigenicity of GC cells in vitro and in vivo. Our results also demonstrated that the molecular mechanisms of the effect of GNA13 in GC included promotion of G1/S cell cycle transition through upregulation of c-Myc, activation of AKT and ERK activity, suppression of FOXO1 activity, upregulation of cyclin-dependent kinase (CDK) regulator cyclin D1 and downregulation of CDK inhibitor p21Cip1 and p27Kip1. Our present study illustrated that GNA13 has an important role in promoting proliferation and tumorigenicity of GC, and may represent a novel prognostic biomarker and therapeutic target for this disease.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.|Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.|Department of Ultrasound, Cancer Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yun
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Jie-Wei
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Weng
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Zou-San
authors.initials: ZS
authors.lastname: Zheng
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Cui
authors.initials: C
authors.lastname: Chen
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002453:Cell Cycle; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D044365:GTP-Binding Protein alpha Subunits, G12-G13
keywords: GNA13; gastric cancer; proliferation; tumorigenicity