Gli1与β-catenin相互作用促进二者在结肠癌细胞中的协同核输入

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. LiCl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.

Interaction between Gli1 and β-Catenin for the Synergized Nuclear Import in Colon Cancer Cells

Wnt and Hedgehog（Hh）signaling play key roles in embryonic and stem cell development, as well as in colon cancer recurrence and invasion. However, the interplay of these two pathways are not well understood. Here, we demonstrated a protein protein interaction between glioma-associated oncogene homolog 1( Gli1) and β-catenin of the two pathways, which contributed to their nuclear transport. The expression of Gli1 and β-catenin were upregulated in colon cancer cells. Activation of Wnt signaling by LiCl increased Gli1 expression; β-catenin RNAi decreased Gli1 levels. Gli1 over expression increased intracellular β-catenin. GANT61 or Gli1 siRNA transfection decreased β-catenin. The results suggested that nuclear import of Gli1 and β-catenin might alter the crosstalk between Hedgehog and Wnt signaling, which contributed to colorectal cancer progression.