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Wnt信号通路和Hedgehog(Hh)信号通路在胚胎和干细胞的发育中发挥重要作用.此外,这两条信号途径在结肠癌复发和浸润的过程也至关重要.然而,Wnt信号通路、Hedgehog信号通路二者之间具体的交互作用机制目前仍不清楚.本文发现,这两条途径的关键分子Gli1和β-联蛋白之间存在蛋白质相互作用.Gli1与β-联蛋白之间的分子相互作用有助于二者的核输入.同时发现,在肠癌细胞系中,Gli1与β-联蛋白协同上调表达.Li Cl激活细胞Wnt信号通路使Gli1表达水平增加,RNA干扰抑制Wnt信号通路,Gli1的表达水平下降.同时,Gli1的过表达也提高了细胞内β-联蛋白的表达水平,并且用Hedgehog信号通路抑制剂GANT61处理细胞,降低Gli1的表达后细胞内β-联蛋白的表达相应下降.本研究揭示了Gli1和β-联蛋白的相互作用及二者协助核输入在Wnt、Hedgehog信号通路交互调节中发挥重要作用,Wnt、Hedgehog信号通路交互作用为大肠癌发生发展研究提供了细胞水平交互调控机制.
Wnt signaling pathway and Hedgehog (Hh) signaling pathway play important roles in the development of embryonic and stem cells. In addition, these two signaling pathways are also critical in the process of colon cancer recurrence and infiltration. However, Wnt signaling pathway, Hedgehog signaling pathway The specific interaction mechanism between the two remains unclear. It is found that there are protein interactions between the key molecules Gli1 and β-catenin of these two pathways. There are molecular interactions between Gli1 and β-catenin. Assists in the nuclear import of both. It was also found that Gli1 cooperates with β-catenin to up-regulate expression in colon cancer cell lines. LiCl activates Wnt signaling pathway to increase Gli1 expression, RNA interference inhibits Wnt signaling pathway, and Gli1 The expression level was decreased. At the same time, overexpression of Gli1 also increased the expression of β-catenin in the cells, and treatment of cells with Hedgehog signaling pathway inhibitor GANT61 reduced the expression of β-catenin in cells after decreasing Gli1 expression. This study revealed that the interactions of Gli1 and β-catenin and their contribution to nuclear import play an important role in the interactive regulation of Wnt and Hedgehog signaling pathways, and Wnt and Hedgehog signaling pathway interactions. The role of the study for the development of colorectal cancer provides a cellular level interactive regulation mechanism.