Overexpression of RhoV Promotes the Progression and EGFR-TKI Resistance of Lung Adenocarcinoma

RhoV过表达促进肺腺癌进展及EGFR-TKI耐药

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作者:Hongjin Chen, Ruixue Xia, Long Jiang, Yong Zhou, Haojun Xu, Weiwei Peng, Chengyun Yao, Guoren Zhou, Yijie Zhang, Hongping Xia, Yongsheng Wang

Background

The Rho GTPase family with ~20 member genes play central roles in a wide variety of cellular processes and tumor cell migration and metastasis. Different Rho GTPase may play different roles in the progression of lung adenocarcinoma.

Conclusion

Overexpression of RhoV in lung adenocarcinoma promotes the progression and EGFR-TKI resistance, suggesting RhoV is a promising prognosis and therapeutic target of lung adenocarcinoma.

Methods

We comprehensively examined the expression of all Rho GTPase family member genes in a panel of lung adenocarcinoma patient's tumors and matched normal tissues. We next investigated the critical role of RhoV in different lung adenocarcinoma cells and animal models.

Results

RhoV was identified as one of the most significantly overexpressed Rho GTPases in lung adenocarcinoma and associated with patients' survival. Silencing RhoV expression inhibits proliferation, migration and invasion, and tumorigenicity capacities of lung adenocarcinoma cells. Moreover, knockdown RhoV promoted the sensitivity of EGFR-TKI in the gefitinib resistant PC9 cells (PC9-GR) and aggravated gefitinib-induced lung cancer cell apoptosis both in PC9 and PC9-GR cells. Our data also indicated that RhoV induced progression and EGFR-TKI resistance of lung adenocarcinoma may be related to the activation of the AKT/ERK pathway.

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