Oncotarget

Research Papers:

c-Src activation promotes nasopharyngeal carcinoma metastasis by inducing the epithelial-mesenchymal transition via PI3K/Akt signaling pathway: a new and promising target for NPC

Liangru Ke, Yanqun Xiang, Xiang Guo, Jinping Lu, Weixiong Xia, Yahui Yu, Yongjian Peng, Li Wang, Gang Wang, Yanfang Ye, Jing Yang, Hu Liang, Tiebang Kang and Xing Lv _

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Oncotarget. 2016; 7:28340-28355. https://doi.org/10.18632/oncotarget.8634

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Abstract

Liangru Ke1,2,*, Yanqun Xiang1,2,*, Xiang Guo1,2,*, Jinping Lu4, Weixiong Xia1,2, Yahui Yu1,2, Yongjian Peng2, Li Wang2, Gang Wang2, Yanfang Ye3, Jing Yang1,2, Hu Liang1,2, Tiebang Kang2, Xing Lv1,2

1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

2Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China

3Department of Biostatistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, China

4Medical Research Center and Clinical Laboratory, Zhuhai Hospital, Jinan University, Zhuhai People’s Hospital, Zhuhai, China

*These authors contributed equally to this work

Correspondence to:

Xing Lv, email: [email protected]

Tiebang Kang, email: [email protected]

Keywords: nasopharyngeal carcinoma, metastasis, c-Src activation, therapy target, epithelial-mesenchymal transition

Received: June 14, 2015     Accepted: March 18, 2016     Published: April 07, 2016

ABSTRACT

Aberrant activation of cellular Src (c-Src), a non-receptor tyrosine kinase, could promote cancer progression through activating its downstream signaling pathways. However, the roles of c-Src and phosphorylated-Src (p-Src) in nasopharyngeal carcinoma (NPC) progression are rarely investigated. Herein, we have identified high c-Src concentrations in the serum of NPC patients with distant metastasis using high-throughput protein microarrays. Levels of c-Src in serum and p-Src in human primary NPC samples were unfavorable independent prognostic factors for cancer-specific survival, disease-free survival, and distant metastasis-free survival. Depletion or inactivation of c-Src in NPC cells using sgRNA with CRISPR/Cas9 system or PP2 decreased cell viability, colony formation, migration and invasion in vitro and metastasis in vivo. In contrast, these malignancies could be up-regulated by overexpressed c-Src in a NPC cell line with low-metastasis potential. Furthermore, p-Src was involved in promoting NPC cell metastasis by inducing the epithelial-mesenchymal transition (EMT) process via activating the PI3K/Akt pathway and cytoskeleton remodeling. The p-Src-induced EMT process could be retarded by PP2, which mediated by down-regulating the PI3K/Akt pathway. In conclusion, elevated levels of c-Src in serum and p-Src in primary NPC tissue correlated with poor outcomes of NPC patients. And aberrant activation of c-Src facilitated NPC cells with malignant potential, especially metastasis ability, which mediated by the PI3K/Akt pathway activation and sequentially induced the EMT process. These findings unveiled a promising approach for targeted therapy of advanced NPC.


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