神经药理学报

神经药理学报 ›› 2021, Vol. 11 ›› Issue (3): 50-64.DOI: 10.3969/j.issn.2095-1396.2021.03.009

• 综述 • 上一篇    

黏着斑激酶在疾病发生发展过程中的作用研究进展

贺巾钊，杨宝学   

  1. 天然药物及仿生药物国家重点实验室，北京大学基础医学院药理学系，北京，100191，中国
  • 出版日期:2021-06-26 发布日期:2021-02-26
  • 通讯作者: 杨宝学，男，博士生导师，中国药理学会常务理事、肾脏药理学专业委员会主委；研究方向：药理学；Tel：+86-010-82825622，E-mail：baoxue@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金重点国际合作研究项目（No.81620108029），国家自然科学基金重点项目（No.81330074），国家自然科学基金面
    上项目（No.81974083）

Studies on the Role of Focal Adhesion Kinase in Diseases

HE Jin-zhao，YANG Bao-xue   

  1. State Key Laboratory of Natural and Biomimetic Drugs ＆ Department of Pharmacology，School of Basic Medical Sciences，Peking University，Beijing，100191，China
  • Online:2021-06-26 Published:2021-02-26

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摘要：

黏着斑激酶（focal adhesion kinase，FAK）是组成黏着斑（focal adhesions，FAs）的关键蛋白，参与连接细胞外基质环境和细胞内信号。FAK 作为一种非受体型酪氨酸激酶，受整合素、生长因子受体、G 蛋白耦联受体等调控，介导多种生理活动，如细胞迁移、侵袭、增殖、分化、血管生成等。研究表明，FAK 异常表达及活化在心血管、肝脏、肾脏、脂肪代谢、免疫调节等相关疾病发生过程中发挥重要作用，且与癌症预后相关。近年来随着对FAK 动物模型及小分子抑制剂的研究深入，靶向于FAK 为治疗多种疾病提供了新的手段。FAK 小分子抑制剂呈现良好的临床前疗效且无明显副作用，其中多种小分子抑制剂已进入临床试验。该文综述了FAK 在多种组织器官疾病发生发展中的作用及其抑制剂在相关研究中的使用，阐述现阶段以FAK 作为治疗疾病靶点的作用机制及应用前景。

关键词: 黏着斑激酶, Src 蛋白, FAK 抑制剂, 癌症

Abstract:

Focal adhesion kinase （FAK） as a crucial component of focal adhesions （FAs） plays an important role in intracellular and extracellular signal transduction. FAK is a non-receptor tyrosine kinase and mainly regulated by integrins，growth factors and G-protein-coupled receptors，which mediates various bioactivities，such as cell migration，invasion，proliferation，differentiation and angiogenesis. A wide array of studies have demonstrated that abnormal expression and activation of FAK were critically involved in the pathogenesis of cardiovascular diseases，hepatic and renal injuries，lipometabolism，immunoregulation and cancer，in which were closely related to poor prognosis. In recent years，with the development of FAK animal models and inhibitors，targeting FAK has been recognized as new treatment for diseases. Most FAK inhibitors show promising preclinical effect
without significant adverse effect and several are undergoing clinical trials. This review summarizes the studies on the role of FAK in diseases and related animal models and inhibitors to clarify the underlying mechanism and therapeutic prospect.

Key words: focal adhesion kinase, Src protein, FAK inhibitor, cancer

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