GNA13 as a prognostic factor and mediator of gastric cancer progression.
GNA13 as a prognostic factor and mediator of gastric cancer progression.
复制标题
GNA13 作为胃癌进展的预后因素和介质。
DOI：
10.18632/oncotarget.6780
复制
发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Ye S
中科院分区：
文献类型：
--
作者：
Zhang JX;Yun M;Xu Y;Chen JW;Weng HW;Zheng ZS;Chen C;Xie D;Ye S
鸟嘌呤核苷酸结合蛋白（G蛋白）α 13（GNA 13）已被认为是几种人类癌症中的致癌蛋白。在这项研究中，GNA 13的特点是其在胃癌（GC）的进展和潜在的分子机制的作用。通过免疫组织化学（IHC）在两个独立的GC样品组中检查GNA 13的表达动力学。通过一系列的体内和体外实验研究GNA 13在胃癌中的作用及其机制。在两组GC样本中，我们观察到GNA 13在GC组织中显著过表达，并且与GC进展的侵袭性程度和患者的生存率差密切相关。进一步的研究表明，GNA 13表达的上调通过促进细胞生长速率、集落形成和裸鼠中的肿瘤形成，在体外和体内增加GC细胞的增殖和致瘤性。相反，GNA 13的敲低在体外和体内有效地抑制了GC细胞的增殖和致瘤性。GNA 13对胃癌细胞的作用机制可能是通过上调c-Myc、激活AKT和ERK活性、抑制FOXO 1活性、上调细胞周期蛋白依赖性激酶（cyclin-dependent kinase，CDK）调节因子cyclinD 1和下调CDK抑制因子p21 Cip 1和p27 Kip 1，从而促进G1/S细胞周期转换。我们的研究表明，GNA 13在促进胃癌的增殖和致瘤性方面具有重要作用，可能代表这种疾病的新的预后生物标志物和治疗靶点。
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.