Wnt抑制因子-1与Wnt通路和肿瘤发生

Wnt抑制因子-1(WntInhibitoryFactor-1,WIF-1)是近年发现的一种Wnt信号抑制分子。WIF-1的结构已基本清楚,其在生物体内的分布因种属和不同发育时期而异。目前认为,WIF-1可能是Wnt的负反馈调节因子,它可与WNT蛋白直接结合并阻断Wnt信号的传递,而Wnt信号也可通过反馈机制对WIF-1的表达和分布进行调节。研究证实,Wnt通路紊乱可引起肿瘤,在多种存在Wnt通路紊乱的肿瘤中均存在WIF-1表达下调或缺失,WIF-1表达下调的原因是由于wif-1基因启动子区发生高甲基化,采用去甲基化等方法恢复WIF-1的正常表达后可抑制相关肿瘤细胞的生长,甚至导致凋亡。

Wnt Inhibitory Factor-1, the Wnt Signal Transduction and Oncogenesis

WIF-1 is a Wnt antagonist discovered in recent years.The structure of the WIF-1 has been essentially understood.In vivo distribution of WIF-1 in vivo varies with genus and stage of development.It is believed that WIF-1 may function as a feedback inhibitor of Wnt signaling and WIF-1 can inhibit Wnt signaling by directly binding to Wnt molecules.Wnt singaling can regulate the WIF-1 by some feedback mechanisms.Researches have confirmed that the disorder of the Wnt singal transtruction can lead to tumor development and the expression of WIF-1 was reduced or lost in the tumor in which the Wnt singaling is out of order in comparison with corresponding normal tissue.The deregulated expression of WIF-1 is associated with the hypermethylation of its promoter.Restoring the expression of WIF-1 by demethylation can repress the growth or induce apoptosis of tumor cells.