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

被引:21
作者
Chen, Hongjin [1 ,2 ,3 ]
Xia, Ruixue [4 ]
Jiang, Long [5 ]
Zhou, Yong [6 ]
Xu, Haojun [1 ,2 ,3 ]
Peng, Weiwei [7 ,8 ,9 ]
Yao, Chengyun [7 ,8 ,9 ]
Zhou, Guoren [7 ,8 ,9 ]
Zhang, Yijie [4 ]
Xia, Hongping [1 ,2 ,3 ,4 ,7 ,8 ,9 ]
Wang, Yongsheng [6 ]
机构
[1] Nanjing Med Univ, Dept Pathol, Sch Basic Med Sci, Nanjing, Peoples R China
[2] Nanjing Med Univ, Sir Run Run Hosp, Nanjing, Peoples R China
[3] Nanjing Med Univ, Key Lab Antibody Tech, Natl Hlth Commiss, Nanjing, Peoples R China
[4] Henan Univ, Dept Resp & Crit Care Med, Huaihe Hosp, Kaifeng, Peoples R China
[5] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Lung Canc Ctr, Shanghai, Peoples R China
[6] Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Nanjing, Peoples R China
[7] Nanjing Med Univ, Jiangsu Canc Hosp, Nanjing, Peoples R China
[8] Nanjing Med Univ, Affiliated Canc Hosp, Nanjing, Peoples R China
[9] Jiangsu Inst Canc Res, Nanjing, Peoples R China
关键词
RhoV; lung adenocarcinoma; gefitinib; AKT; ERK; CANCER; THERAPY; MET;
D O I
10.3389/fonc.2021.619013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background The Rho GTPase family with similar to 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. 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. 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.
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页数:10
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