Wnt, RSPO and Hippo Signalling in the Intestine and Intestinal Stem Cells

Genes
Vitezslav Kriz, Vladimir Korinek

Abstract

In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling. There is growing evidence for multiple crosstalk between Hippo and Wnt/β-catenin signalling. In the ON state, Hippo signalling results in serine/threonine phosphorylation of Yes-associated protein (YAP1) and tafazzin (TAZ), promoting formation of the β-catenin destruction complex. In contrast, YAP1 or TAZ dephosphorylation (and YAP1 methylation) results in β-catenin destruction complex deactivation and β-catenin nuclear localization. In the Hippo OFF state, YAP1 and TAZ are engaged with the nuclear β-catenin and participate in the β-catenin-dependent transcription program. Interestingly, YAP1/TA...Continue Reading

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Citations

Mar 3, 2018·Genes·Jessica PerochonJulia B Cordero
Apr 29, 2019·Cancer Metastasis Reviews·Zhe Wang, Margot Zöller
Oct 17, 2019·Genes·Monika StastnaVladimir Korinek
Dec 6, 2018·Cell Proliferation·Jiuheng YinHua Yang
Jun 21, 2019·International Journal of Molecular Sciences·Sylvester LarsenJesper T Troelsen
Jun 28, 2019·Journal of Drug Targeting·Meng-Yan WangRong-Guang Shao
May 28, 2020·Frontiers in Cell and Developmental Biology·Yong-Ri JinJeong Kyo Yoon
May 1, 2021·Technology in Cancer Research & Treatment·Junjun ShuJun Yang
Mar 25, 2021·American Journal of Physiology. Cell Physiology·Alicia M BarnettNicole C Roy
Jul 3, 2021·International Journal of Molecular Sciences·Shaida Ouladan, Alex Gregorieff

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Methods Mentioned

BETA
transgenic
GTPases
ubiquitination
GTPase
chip
gene knockout
nuclear translocation
co-immunoprecipitation

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