title: Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway.
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.
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors: Chen
authors: C
authors: Lin
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors: Shanshan
authors: S
authors: Wang
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors: Weiwei
authors: W
authors: Xie
authors: Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, P.R. China.
authors: Rongliang
authors: R
authors: Zheng
authors: 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.
authors: Yu
authors: Y
authors: Gan
authors: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors: Jianhua
authors: J
authors: Chang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D011725:Pyridines / Q000627:therapeutic use*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C573239:KIF5B-RET fusion protein, human; D015514:Oncogene Proteins, Fusion; D011725:Pyridines; C553458:apatinib; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D019061:src-Family Kinases
keywords: KIF5B-RET; Src signaling pathway; apatinib; invasion and migration; targeted therapy