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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。
The Hedgehog (Hh) signaling pathway plays a key role in the normal development of the embryo. Recent studies have shown that the Hh signaling pathway is abnormally activated in many tumors. Sufu (suppressor of fused), a regulator of Hh signaling, is commonly expressed in colorectal cancer tissues but not in other key molecules in the pathway. SuFu does not act directly on the transcription factor Gli through Pcth1 and Smo. SuFu in the cytoplasm with Gli to prevent Gli into the nucleus; also in the nucleus of other proteins to help inhibit Gli activity, which negative feedback regulation of Hh signaling. When SuFu gene mutation occurs, its conformation changes, the inhibition of Gli weakened, and make Gli expression increased Hh pathway abnormal activation, promote the development of colorectal cancer. This review summarizes the mechanism of Hh signaling pathway and the relationship between SuFu and colorectal cancer and aims to provide some theoretical basis for the targeted therapy of colorectal cancer.