Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

Chen Lin; Shanshan Wang; Weiwei Xie; Rongliang Zheng; Yu Gan; Jianhua Chang

doi:10.18632/oncotarget.10985

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Research Papers:

Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

Chen Lin, Shanshan Wang, Weiwei Xie, Rongliang Zheng, Yu Gan and Jianhua Chang _

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Oncotarget. 2016; 7:59236-59244. https://doi.org/10.18632/oncotarget.10985

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Abstract

Chen Lin1,*, Shanshan Wang1,*, Weiwei Xie1, Rongliang Zheng2, Yu Gan3, Jianhua Chang1

1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China

2Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, P.R. China

3State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, P.R. China

*These authors contributed equally to this work

Correspondence to:

Jianhua Chang, email: [email protected]

Yu Gan, email: [email protected]

Keywords: apatinib, KIF5B-RET, invasion and migration, Src signaling pathway, targeted therapy

Received: April 23, 2016 Accepted: July 10, 2016 Published: August 01, 2016

ABSTRACT

The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors.

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Research Papers:

Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

Abstract