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. 2019 Dec 16;9:1359. doi: 10.3389/fonc.2019.01359

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Copyright © 2019 Mu, Wang and Zöller.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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LGR5 and the contribution to PaCIC maintenance. (A) The leucine-rich repeat-containing GPCR is engaged in Wnt signaling. Its ligand is R-Spondin. In the absence of R-Spondin, the transmembrane E ligases RNF43/ZNRF3 associate with Frizzled and LRP5/6 that leads to Frizzled phosphorylation and internalization of the complex. (B) However, in the presence of R-Spondin, RNF43/ZNRF3 is recruited toward LGR5 such that Wnt can bind to Frizzled and LRP5/6 becomes phosphorylated. Dsh blocks GSK3-β and β-catenin is liberated to move to the nucleus, where it together with TCF/LEF promotes cMyc, cyclinD1, and Axin1 transcription. Full name of proteins are listed in Table S1. The upregulated expression of LGR5 in PaCIC suggests its engagement in PaCIC maintenance.