Skead Garret, Govender Dhirendra
Division of Anatomical Pathology, University of Cape Town and National Health Laboratory Service, Groote Schuur hospital, Cape Town, South Africa.
J Clin Pathol. 2015 Jun;68(6):405-9. doi: 10.1136/jclinpath-2015-203050. Epub 2015 Apr 22.
The MET receptor tyrosine kinase and its ligand hepatocyte growth factor/scatter factor (HGF/SF) are potential therapeutic targets in many human malignancies, making this pathway an important focus of molecular and cancer research. MET mutations have been detected in various tumours. In addition, many tumour types demonstrate MET and HGF/SF overexpression and amplification. The MET signal transduction cascade is complex, and manifests in a broad spectrum of mitogenic and morphogenic functions, affecting cell proliferation, migration, differentiation, morphology and survival. Cancer cells commandeer the physiological functions of this signalling axis to facilitate invasion and metastasis. Significant progress has been made in the development of agents that inhibit MET-HGF/SF signalling. In this article, we outline the key features of the MET gene, its protein product and the ligand HGF/SF, to provide an overview of this important signalling pathway and offer a summary of the relevant pathological and clinical directions of research.
MET受体酪氨酸激酶及其配体肝细胞生长因子/分散因子(HGF/SF)是许多人类恶性肿瘤潜在的治疗靶点,使得该信号通路成为分子研究和癌症研究的重要焦点。在各种肿瘤中均检测到MET突变。此外,许多肿瘤类型显示出MET和HGF/SF的过表达及扩增。MET信号转导级联反应复杂,表现为广泛的促有丝分裂和形态发生功能,影响细胞增殖、迁移、分化、形态及存活。癌细胞利用该信号轴的生理功能促进侵袭和转移。在抑制MET-HGF/SF信号传导的药物研发方面已取得显著进展。在本文中,我们概述了MET基因、其蛋白质产物及配体HGF/SF的关键特征,以对这一重要信号通路进行综述,并总结相关的病理及临床研究方向。