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即刻早期反应蛋白2通过整合素β1介导的信号通路调节肝癌细胞的黏附和迁移。

Immediate early response protein 2 regulates hepatocellular carcinoma cell adhesion and motility via integrin β1-mediated signaling pathway.

作者信息

Xu Zhengxin, Zhu Lei, Wu Wenjuan, Liao Yuexia, Zhang Weicheng, Deng Zijing, Shen Jingyuan, Yuan Qing, Zheng Lu, Zhang Yu, Shen Weigan

机构信息

School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.

出版信息

Oncol Rep. 2017 Jan;37(1):259-272. doi: 10.3892/or.2016.5215. Epub 2016 Nov 3.

Abstract

Human immediate early response 2 (IER2) has been reported to function as a potential transcriptional factor or transcriptional co‑activator and seems to play a pivotal role in tumor cell motility and metastasis, however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Herein, we demonstrated that overexpression of IER2 in HCC cells increased cell adhesion to fibronectin, migration and invasion, whereas knockdown of IER2 displayed the opposite effects. In agreement with this phenotype, IER2 expression was positively correlated with the metastatic potential and integrin β1 (ITGB1) expression in HCC cell lines. Moreover, we demonstrated a critical role for IER2 in regulation of HCC cell‑extracellular matrix (ECM) adhesion and motility by the transcriptionally promoted ITGB1. Furthermore, we showed that ITGB1‑focal adhesion kinase (FAK)‑Src‑paxillin signal pathway activated by IER2 may contribute to the HCC cell‑ECM adhesion and motility. These results demonstrated that IER2 promoted HCC cell adhesion and motility probably by directly increasing ITGB1 expression and subsequently activating the ITGB1‑FAK‑Src‑paxillin signal pathway.

摘要

据报道,人类即刻早期反应蛋白2(IER2)可作为一种潜在的转录因子或转录共激活因子发挥作用,并且似乎在肿瘤细胞的运动和转移中起关键作用。然而,其在肝细胞癌(HCC)中的作用及潜在机制仍不清楚。在此,我们证明,HCC细胞中IER2的过表达增加了细胞对纤连蛋白的黏附、迁移和侵袭,而IER2的敲低则表现出相反的效果。与这种表型一致,IER2的表达与HCC细胞系中的转移潜能和整合素β1(ITGB1)的表达呈正相关。此外,我们证明IER2通过转录促进ITGB1在调节HCC细胞与细胞外基质(ECM)的黏附及运动中起关键作用。此外,我们表明,IER2激活的ITGB1-黏着斑激酶(FAK)-Src-桩蛋白信号通路可能有助于HCC细胞与ECM的黏附及运动。这些结果表明,IER2可能通过直接增加ITGB1的表达并随后激活ITGB1-FAK-Src-桩蛋白信号通路来促进HCC细胞的黏附及运动。

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