Crosstalk of Hedgehog and mTORC1 Pathways.
Crosstalk of Hedgehog and mTORC1 Pathways.
复制标题
Hedgehog和mTORC1通路的串扰。
DOI：
10.3390/cells9102316
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发表时间：
2020-10-18
期刊：
影响因子：
6
通讯作者：
Møller LB
中科院分区：
文献类型：
--
作者：
Larsen LJ;Møller LB
Hedgehog（Hh）信号和mTOR信号是胚胎发育和细胞代谢所必需的，两者都由初级纤毛协调。来自癌细胞的观察强烈表明Hh和mTOR信号传导之间的串扰。这一假说得到了几项研究的支持：证据表明TGFβ介导的串扰;增加的PI 3 K/AKT/mTOR活性通过调节GLI转录因子导致增加的Hh信号传导;增加的Hh信号传导通过上调NKX2.2正向调节mTORC 1活性，导致负性mTOR调节因子的下调; GSK 3和AMPK作为两条信号通路的成员，是Hh和mTORC 1信号传导之间潜在的重要联系;激酶DYRK 2正向调节Hh信号传导，而mTORC 1负向调节Hh信号传导。相反，对于DYRK 1A和DYRK 1B，Hh的正调控和负调控都被观察到，它们都正调控mTORC 1信号传导。基于纤毛，Hh和mTORC 1之间观察到的串扰，我们认为Hh和mTORC 1之间的相互作用比我们目前的知识更广泛。虽然许多研究集中在串扰已经进行，矛盾的意见出现，涉及多个合作伙伴的相互作用是远远没有解决。
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.
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DOI：
10.1016/j.bbrc.2017.07.107
发表时间：
2017-09-23
影响因子：
3.1
作者：
Ehe BK;Lamson DR;Tarpley M;Onyenwoke RU;Graves LM;Williams KP
通讯作者：
Williams KP
影响因子：
4.8
作者：
Bautista, Stephen J.;Boras, Ivan;Antonescu, Costin N.
通讯作者：
Antonescu, Costin N.
影响因子：
12.4
作者：
Finetti, Francesca;Cassioli, Chiara;Baldari, Cosima T.
通讯作者：
Baldari, Cosima T.
影响因子：
4.8
作者：
Agarwal, Nitin K.;Qu, Changju;Vega, Francisco
通讯作者：
Vega, Francisco
DOI：
10.1007/978-3-030-35582-1_4
发表时间：
2020-01-01
期刊：
TUMOR MICROENVIRONMENT: SIGNALING PATHWAYS, PT A
影响因子：
--
作者：
Bazzichetto, Chiara;Conciatori, Fabiana;Ciuffreda, Ludovica
通讯作者：
Ciuffreda, Ludovica