G3BP1 contributes to tumor metastasis via upregulation of Slug expression in hepatocellular carcinoma.

作者: Jingde Chen , Yandong Li , Ning Dou , Yong Gao , Shijun Yu

DOI:

关键词: Cancer researchCell migrationRNA interferenceBiologyGene knockdownDownregulation and upregulationGene silencingCell Migration InhibitionSlugMetastasis

摘要: RasGAP SH3-domain-Binding Protein 1 (G3BP1) has been implicated in cell growth, migration, and metastasis of some cancers, yet its function hepatocellular carcinoma (HCC) remains to be explored. In the present study, we reported that G3BP1 was upregulated HCC tissues compared with adjacent non-cancerous liver both mRNA protein levels, high expression significantly correlated poor prognosis patients. Functional analyses demonstrated forced cells promoted silenced by RNA interference caused opposite effects. Moreover, knockdown attenuated distant capacity through tail vein injection approach nude mice model. At molecular mechanism, found decreased Slug expression, increased epithelial marker E-cadherin. Overexpression could restore phenotype silencing induced migration inhibition. Together, our data establish as an oncogenic factor involved suggest might serve a novel predictor for patients' outcome.

参考文章(25)
Shao-Hui Cai, Hong-Sheng Wang, Jun Du, Rui Fang, Qiang Guo, Ge Zhang, Mei-Yu Quan, Fen Ning, Endogenous Nodal promotes melanoma undergoing epithelial-mesenchymal transition via Snail and Slug in vitro and in vivo American Journal of Cancer Research. ,vol. 5, pp. 2098- 2112 ,(2015)
Catherine Frenette, Robert Wong, Updates in the management of hepatocellular carcinoma. Gastroenterología y Hepatología. ,vol. 7, pp. 16- 24 ,(2011)
Lingqiang Min, Yuanyuan Ruan, Zhenbin Shen, Dongwei Jia, Xuefei Wang, Junjie Zhao, Yihong Sun, Jianxin Gu, Overexpression of Ras-GTPase-activating protein SH3 domain-binding protein 1 correlates with poor prognosis in gastric cancer patients. Histopathology. ,vol. 67, pp. 677- 688 ,(2015) , 10.1111/HIS.12695
Hao Zhang, Yan Ma, Shenghua Zhang, Hong Liu, Hongwei He, Naren Li, Yuyan Gong, Shuangshuang Zhao, Jian-dong Jiang, Rong-guang Shao, Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells via the Smad signaling pathway Oncotarget. ,vol. 6, pp. 17039- 17053 ,(2015) , 10.18632/ONCOTARGET.3636
Scott D. Briggs, Sophia S. Bryant, Richard Jove, Sam D. Sanderson, Thomas E. Smithgall, The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck Journal of Biological Chemistry. ,vol. 270, pp. 14718- 14724 ,(1995) , 10.1074/JBC.270.24.14718
Katharine Irvine, Renee Stirling, David Hume, Derek Kennedy, Rasputin, more promiscuous than ever: a review of G3BP. The International Journal of Developmental Biology. ,vol. 48, pp. 1065- 1077 ,(2004) , 10.1387/IJDB.041893KI
M M Kim, D Wiederschain, D Kennedy, E Hansen, Z-M Yuan, Modulation of p53 and MDM2 activity by novel interaction with Ras-GAP binding proteins (G3BP). Oncogene. ,vol. 26, pp. 4209- 4215 ,(2007) , 10.1038/SJ.ONC.1210212
Catarina Castro Alves, Fatima Carneiro, Heinz Hoefler, Karl-Friedrich Becker, Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers Frontiers in Bioscience. ,vol. Volume, pp. 3035- ,(2009) , 10.2741/3433
Antonio Garcia de Herreros, Sandra Peiró, Mayssaa Nassour, Pierre Savagner, Snail family regulation and epithelial mesenchymal transitions in breast cancer progression Journal of Mammary Gland Biology and Neoplasia. ,vol. 15, pp. 135- 147 ,(2010) , 10.1007/S10911-010-9179-8
XIULAN ZHAO, BAOCUN SUN, DAN SUN, TIEJU LIU, NA CHE, QIANG GU, XUEYI DONG, RUI LI, YANRONG LIU, JING LI, Slug promotes hepatocellular cancer cell progression by increasing sox2 and nanog expression Oncology Reports. ,vol. 33, pp. 149- 156 ,(2015) , 10.3892/OR.2014.3562