Oncotarget

Research Papers:

The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis

Tian-Hao Liu _, Fang Zheng, Mu-Yan Cai, Lin Guo, Huan-Xin Lin, Jie-Wei Chen, Yi-Ji Liao, Hsiang-Fu Kung, Yi-Xin Zeng and Dan Xie

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:25836-25848. https://doi.org/10.18632/oncotarget.8283

Metrics: PDF 2170 views  |   HTML 1746 views  |   ?  


Abstract

Tian-Hao Liu1,2,*, Fang Zheng1,3,*, Mu-Yan Cai1,5,*, Lin Guo1,4, Huan-Xin Lin1, Jie-Wei Chen1,5, Yi-Ji Liao1, Hsiang-Fu Kung1, Yi-Xin Zeng1, Dan Xie1,5

1Sun Yat-Sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

2Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China

3Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

4Department of Nasopharyngeal Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China

5Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Dan Xie, e-mail: [email protected]

Keywords: nasopharyngeal carcinoma, ARHGEF3, BIRC8, apoptosis, pathogenesis

Received: September 06, 2015    Accepted: March 06, 2016    Published: March 23, 2016

ABSTRACT

Nasopharyngeal carcinoma (NPC) is one of the most prevalent forms of highly invasive malignancy in Southern China and Southeast Asia. The pathogenesis of NPC is a multistep process driven by the acquisition of numerous genetic abnormalities. We investigated the potential oncogenic role of the Rho-guanine nucleotide exchange factor 3 gene, ARHGEF3, in NPC pathogenesis. Expression levels of ARHGEF3 were frequently up-regulated in NPC cell lines and tissues. In a large cohort of clinical NPC tissues high expression of ARHGEF3 was positively associated with an increased T status, distant metastasis, and a more advanced clinical stage (P < 0.05). Survival analysis revealed that ARHGEF3 expression was a significant and independent prognosis factor for NPC patients. In NPC cell lines, knockdown of ARHGEF3 was sufficient to inhibit cell growth, motility, and invasion in vitro, whereas ectopic overexpression of ARHGEF3 substantially enhanced NPC cells tumorigenesis and metastasis in vivo. Depletion of ARHGEF3 in NPC cells dramatically promoted caspase-3 induced apoptosis and an anti-apoptosis factor, BIRC8, was identified as a critical downstream target of the ARHGEF3. Our findings suggest that increased expression of ARHGEF3 plays a critical oncogenic role in NPC pathogenesis by preventing cell apoptosis through the up-regulation of BIRC8, and ARHGEF3 might be employed as a novel prognostic marker and effective therapeutic target for human NPC.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8283