四跨膜蛋白超家族Tetraspanins在肿瘤及纤维化疾病中的作用概况

Role of Tetraspanins in Treatment of Tumor and Fibrosis:a Literature Review

Tetraspanins是四跨膜蛋白超家族(Transmembrane 4 Superfamily,TM4SF),可以与自身和/或细胞表面分子如整合素,免疫球蛋白超家族蛋白,蛋白酶,生长因子受体和细胞内信号分子相结合形成四跨膜蛋白网络(Tetraspanin Enriched Microdomains,TEMs),调节细胞信号转导,细胞粘附、迁移、增殖、分化等生理过程。Tetraspanins通过影响肿瘤细胞的迁移、侵袭、血管生成、上皮细胞间质转化(Epithelial Mesenchymal Transition,EMT),进而参与肿瘤的发生发展。纤维化疾病与肿瘤的发病机制存在很多相似之处。近年来,有研究发现Tetraspanins在纤维化疾病如肝纤维化及肺纤维化中同样起着重要作用。为进一步加深对Tetraspanins在疾病中的认识,文章主要对Tetraspanins的结构、基本生物学功能、组织分布及其在肿瘤和纤维化疾病中的作用进行阐述,将有助于对肿瘤及纤维化疾病发病机制的理解,并为疾病的深入研究及探索新的治疗药物提供理论依据。

Tetraspanins belong to transmembrane 4 superfamily(TM4SF).They can form tetraspanin-enriched microdomains(TEMs)by combining with itself and/or cell surface markers(such as integrins,immunoglobulin superfamily proteins,protease,growth factor receptor)and intracellular signaling molecules to regulate cell signal transduction,and cell adhesion,migration,proliferation and differentiation.Tetraspanins are involved in the development of tumors by regulating cell migration,invasion,angiogenesis and epithelial mesenchymal transition(EMT).Pathogenesis of fibrosis is similar to tumors in many respects.In recent years,several studies have found that Tetraspanins also play an equally significant role in fibrosis such as liver fibrosis and pulmonary fibrosis.In order to further understand the role of tetraspanins in diseases,this article will mainly elaborate the structure,fundamental biological functions,tissue distribution and biological roles of Tetraspanins,and its role in formation of tumors and fibrosis.This review will help to understand pathogenesis of tumors and fibrosis and provide theoretical basis for further study on developing new therapeutic drugs.