Lee, YA;
Noon, LA;
Akat, KM;
Ybanez, MD;
Lee, T-F;
Berres, M-L;
Fujiwara, N;
... Friedman, SL; + view all
(2018)
Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap.
Nature Communications
, 9
, Article 4962. 10.1038/s41467-018-07338-z.
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Abstract
Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activation of the p62/Sqstm1-Nrf2 axis. Here, we show that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis. Hepatocyte-specific deletion of Atg7 promotes liver size, fibrosis, progenitor cell expansion, and hepatocarcinogenesis, which is rescued by concurrent deletion of Yap. Our results shed new light on mechanisms of Yap degradation and the sequence of events that follow disruption of autophagy, which is impaired in chronic liver disease.
| Type: | Article |
|---|---|
| Title: | Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-07338-z |
| Publisher version: | https://doi.org/10.1038/s41467-018-07338-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10072378 |
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