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

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

doi:10.3892/or.2016.5215

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

Authors:
- Zhengxin Xu
- Lei Zhu
- Wenjuan Wu
- Yuexia Liao
- Weicheng Zhang
- Zijing Deng
- Jingyuan Shen
- Qing Yuan
- Lu Zheng
- Yu Zhang
- Weigan Shen
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Affiliations: School of Medicine, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: November 3, 2016 https://doi.org/10.3892/or.2016.5215
Pages: 259-272

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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.

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