Hedgehog (Hh) signaling and mTOR signaling, essential for embryonic development and cellular metabolism, are both coordinated by the primary cilium. Observations from cancer cells strongly indicate crosstalk between Hh and mTOR signaling. This hypothesis is supported by several studies: Evidence points to a TGFβ-mediated crosstalk; Increased PI3K/AKT/mTOR activity leads to increased Hh signaling through regulation of the GLI transcription factors; increased Hh signaling regulates mTORC1 activity positively by upregulating NKX2.2, leading to downregulation of negative mTOR regulators; GSK3 and AMPK are, as members of both signaling pathways, potentially important links between Hh and mTORC1 signaling; The kinase DYRK2 regulates Hh positively and mTORC1 signaling negatively. In contrast, both positive and negative regulation of Hh has been observed for DYRK1A and DYRK1B, which both regulate mTORC1 signaling positively. Based on crosstalk observed between cilia, Hh, and mTORC1, we suggest that the interaction between Hh and mTORC1 is more widespread than it appears from our current knowledge. Although many studies focusing on crosstalk have been carried out, contradictory observations appear and the interplay involving multiple partners is far from solved.

中文翻译：

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刺猬与mTORC1通路的串扰

刺猬（Hh）信号传导和mTOR信号传导对胚胎发育和细胞代谢至关重要，两者均由初级纤毛协调。癌细胞的观察结果强烈表明Hh和mTOR信号传导之间存在串扰。该假设得到了多项研究的支持：证据表明TGFβ介导的串扰；PI3K / AKT / mTOR活性的增加通过调节GLI转录因子导致Hh信号的增加；Hh信号增强通过上调NKX2.2积极调节mTORC1活性，导致负mTOR调节器的下调；作为两个信号传导途径的成员，GSK3和AMPK都是Hh和mTORC1信号传导之间潜在的重要链接。DYRK2激酶可正向调节Hh，而mTORC1则负向调节。相反，对于DYRK1A和DYRK1B，已观察到Hh的正向和负向调节，两者均正向调节mTORC1信号。根据纤毛，Hh和mTORC1之间观察到的串扰，我们认为Hh和mTORC1之间的相互作用比我们目前所知的更为广泛。尽管已经进行了许多有关串扰的研究，但是出现了相互矛盾的观察，涉及多个伙伴的相互作用还远远没有解决。