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Hedgehog信号通路在肝细胞癌中的作用及其与肿瘤微环境的关系

张晓华 冯颖 王宪波

引用本文:
Citation:

Hedgehog信号通路在肝细胞癌中的作用及其与肿瘤微环境的关系

DOI: 10.12449/JCH240429
基金项目: 

国家中医药管理局高水平中医药重点学科建设项目 (zyyzdxk-2023005);

首都卫生发展科研专项 (2024-1-2173)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王宪波负责课题设计、拟定写作思路;张晓华负责撰写论文;冯颖指导撰写文章并最后定稿。
详细信息
    通信作者:

    王宪波, wangxb@ccmu.edu.cn (ORCID: 0000-0002-3593-5741)

Role of the Hedgehog signaling pathway in hepatocellular carcinoma and its tumor microenvironment

Research funding: 

State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project of Traditional Chinese Medicine (zyyzdxk-2023005);

Capital Health Development Research Project (2024-1-2173)

More Information
    Corresponding author: WANG Xianbo, wangxb@ccmu.edu.cn (ORCID: 0000-0002-3593-5741)
  • 摘要: Hedgehog(Hh)信号通路在肝细胞癌的发生发展和肿瘤微环境中发挥重要作用。Hh信号异常激活可加速肿瘤的生长。Hh信号通路和肿瘤微环境之间的相互串扰与肿瘤的生长和抑制性肿瘤微环境的形成密切相关。有证据表明,抑制Hh信号在抑制肝细胞癌生长中发挥重要作用。本文就Hh信号异常激活在肝细胞癌和肝癌肿瘤微环境中作用及机制的研究现状与潜在的治疗意义作一综述,为肝癌的治疗提供新的思路。

     

  • 图  1  肝癌TME中的Hh信号转导

    注: 当没有Hh配体蛋白时,Ptch能释放抑制Smo活性的蛋白,从而阻滞Smo的激活,使得Hh信号通路关闭。而当Hh配体蛋白(SHH、IHH或DHH)与Ptch结合后,Ptch停止分泌,Smo解除抑制,Hh信号系统被激活,最终导致Gli转录因子成员的激活、向细胞核转移,上调Hh通路下游靶基因如VEGF、Myc、Cyclin D等,从而促进肿瘤增殖、侵袭、转移等;细胞中的Hh信号能驱动肿瘤间质中肿瘤相关巨噬细胞(TAM)的M2极化,抑制CD8+T淋巴细胞功能,从而促进肿瘤的生长;细胞中异常激活的Hh信号和肿瘤相关成纤维细胞(CAF)相互作用并协同促进肿瘤的发展。

    Figure  1.  Hh signal transduction in TME of hepatocellular carcinoma

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  • 收稿日期:  2023-06-28
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