Hedgehog通路分子SuFu在结直肠癌中的作用

Hedgehog signaling pathway member SuFu in colorectal cancer

Hedgehog(Hh)信号通路在胚胎的正常发育过程中发挥关键作用,近年研究表明Hh信号通路在多种肿瘤中异常激活。Hh信号通路中的调控分子SuFu(suppressor of fused)在结直肠癌组织中普遍表达,而通路中其他关键分子并不存在此现象。SuFu可不通过Pcth1和Smo直接作用于转录因子Gli。SuFu在胞质中与Gli结合,阻止Gli进入细胞核;也可在细胞核内辅助其他蛋白抑制Gli的活性,从而负反馈调控Hh信号通路。当SuFu基因发生突变时,其构象改变,对Gli的抑制作用减弱,而且使得Gli的表达增加,Hh通路异常激活,促进结直肠癌的发生发展。本文综述了Hh信号通路的作用机制以及SuFu分子与结直肠癌的关系,旨在为结直肠癌的靶向治疗积累一定的理论基础。

Hedgehog（Hh） signaling pathway plays a critical role in the normal development of embryogenesis. Studies suggest that Hh signaling pathway is aberrantly activated in many kinds of tumors recently. Sufu（Suppressor of fused）, the regulator molecule of Hh signaling pathway, is commonly expressed in colorectal cancer tissue, completely different to other key members of this pathway. Sufu affects the transcription factors Gli directly, regardless of PTCH1 and Smo. Sufu binds with Gli in the cytoplasm preventing Gli from nucleus; it also can assist other proteins in nucleus in inhibiting activity of Gli, thus negatively regulating the Hh signaling pathway. When mutations occur in the SuFu, its conformation will change and the inhibition of Gli is weakened; then the increased expression of Gli and abnormally activated Hh pathway promote the carcinogenesis and development of colorectal cancer. This article has reviewed the mechanism of Hh signaling pathway and the association between Sufu and colorectal cancer, which has certain reference significance for colorectal cancer targeted therapy.