Parikh Rahul A, Wang Peng, Beumer Jan H, Chu Edward, Appleman Leonard J
Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Division of Medical Oncology, University of Kentucky College of Medicine, Markey Cancer Center, Lexington, KY, USA.
Onco Targets Ther. 2014 Jun 11;7:969-83. doi: 10.2147/OTT.S40241. eCollection 2014.
MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepatocyte growth factor (HGF) receptor, a member of the receptor tyrosine kinase (RTK) family. HGF, also known as scatter factor (SF), is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis), mobility (motogenesis), and differentiation (morphogenesis); it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development.
MET基因位于7号染色体长臂31区，是一种原癌基因，编码肝细胞生长因子（HGF）受体，属于受体酪氨酸激酶（RTK）家族成员。HGF也被称为分散因子（SF），是已知的MET唯一配体。MET是细胞生长和分裂（有丝分裂）、迁移（运动发生）及分化（形态发生）的主要调节因子；在正常发育和组织再生中发挥重要作用。在癌症中，HGF-MET轴常因MET基因扩增、易位和突变，或MET或HGF蛋白过表达而失调。MET失调与多种肿瘤类型发生转移的倾向增加及总体预后不良相关。靶向失调的HGF-MET通路是一个活跃的研究领域；多种针对HGF和MET的单克隆抗体以及MET小分子抑制剂正在研发中。本综述总结了HGF-MET轴的关键生物学特性、其在癌症中的失调情况以及正在研发的靶向HGF-MET轴的治疗药物。
