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

// Chen Lin 1, * , Shanshan Wang 1, * , Weiwei Xie 1 , Rongliang Zheng 2 , Yu Gan 3 , Jianhua Chang 1 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China 2 Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, P.R. China 3 State 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: changjianhua@163.com Yu Gan, email: ganyu@shSCI.org 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.