Ras Raf Mek Erk信号传导通路在肝细胞癌发生中的作用机制及在靶向治疗中的应用

Role of the Ras/Raf/Mek/Erk Signal Transduction Pathway in the Mechanism of Hepatocellular Carcinoma Occurrence and Its Significance in Corresponding Targeted Therapy

肝细胞癌(HCC)是我国原发性肝癌最常见的一种类型,也是全球癌性死亡中最重要的一个因素。因此,研究肿瘤生长的细胞机制对于探索新的有效治疗方法非常重要。目前已知,所有真核细胞中均存在Ras/Raf/Mek/Erk这一高度保守的细胞信号传导通路,这一信号传导通路广泛参与细胞的生长、增殖、分化、凋亡、转移等过程。Ras/Raf/Mek/Erk信号传导通路是"MAPK"众多通路中的一个,它在多种致瘤性疾病中通常是上调的。同样,该信号传导通路的异常激活与肝细胞癌的发生及恶性进展密切相关。Ras基因的突变,EGF、VEGF、PDGF等生长因子及相应的膜受体过度表达均可使其激活,诱导肝癌细胞异常增殖,侵袭生长和转移,从而参与和促进肝细胞癌的发生、发展。因此,抑制Ras/Raf/Mek/Erk信号通路的传导将成为肝细胞癌的一种有效治疗方法。

Hepatocellular carcinoma （HCC） is the most common primary liver cancer and is a significant cause of cancer-related death throughout the world. Therefore, studies investigating cellular mechanisms of HCC are essential for developing effective therapies. As we all know, the Ras/Raf/Mek/Erk signaling pathway is a highly conserved module that extensively participates in cell growth, proliferation, differentiation, apoptosis, and migration. The Ras/Raf/Mek/Erk signaling cascade is one of numerous MAPK signal transduction pathways that are frequently deregulated in tumourigenic diseases. In addition, aberrant activation of the Ras/Raf/Mek/ Erk pathway has been shown to be involved in the pathogenesis and progression of HCC. Mutation of the Ras gene and the overexpression of growth factors including EGF, VEGF, PDGF and the homologous mem- brane receptors result in aberrant activation of the Ras/Raf/Mek/Erk pathway, which in turn induces abnormal proliferation, invasive growth and metastasis of HCC. In this manner the R, as/Raf/Mek/Erk pathway partici- pates in and promotes the pathogenesis and progression of HCC. Therefore, inhibition of Ras/Raf/Mek/Erk signaling may be an effective therapy for HCC.