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Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease
The E3 ubiquitin-ligases are important for cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584894/ https://www.ncbi.nlm.nih.gov/pubmed/36266428 http://dx.doi.org/10.1038/s41598-022-22295-w |
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author | Roca-Lema, Daniel Quiroga, Macarena Khare, Vineeta Díaz-Díaz, Andrea Barreiro-Alonso, Aida Rodríguez-Alonso, Andrea Concha, Ángel Romay, Gabriela Cerdán, M. Esperanza Gasche, Christoph Figueroa, Angélica |
author_facet | Roca-Lema, Daniel Quiroga, Macarena Khare, Vineeta Díaz-Díaz, Andrea Barreiro-Alonso, Aida Rodríguez-Alonso, Andrea Concha, Ángel Romay, Gabriela Cerdán, M. Esperanza Gasche, Christoph Figueroa, Angélica |
author_sort | Roca-Lema, Daniel |
collection | PubMed |
description | The E3 ubiquitin-ligases are important for cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer, however, the implication in colitis-associated cancer is unknown. Here, we investigated the potential role of Hakai in intestinal inflammation and cancer bowel disease. Several mouse models of colitis and associated cancer were used to analyse Hakai expression by immunohistochemistry. We also analysed Hakai expression in patients with inflamed colon biopsies from ulcerative colitis and Crohn's disease. By Hakai interactome analysis, it was identified Fatty Acid Synthase (FASN) as a novel Hakai-interacting protein. Moreover, we show that Hakai induces FASN ubiquitination and degradation via lysosome, thus regulating FASN-mediated lipid accumulation. An inverse expression of FASN and Hakai was detected in inflammatory AOM/DSS mouse model. In conclusion, Hakai regulates FASN ubiquitination and degradation, resulting in the regulation of FASN-mediated lipid accumulation, which is associated to the development of inflammatory bowel disease. The interaction between Hakai and FASN may be an important mechanism for the homeostasis of intestinal barrier function and in the pathogenesis of this disease. |
format | Online Article Text |
id | pubmed-9584894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95848942022-10-22 Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease Roca-Lema, Daniel Quiroga, Macarena Khare, Vineeta Díaz-Díaz, Andrea Barreiro-Alonso, Aida Rodríguez-Alonso, Andrea Concha, Ángel Romay, Gabriela Cerdán, M. Esperanza Gasche, Christoph Figueroa, Angélica Sci Rep Article The E3 ubiquitin-ligases are important for cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer, however, the implication in colitis-associated cancer is unknown. Here, we investigated the potential role of Hakai in intestinal inflammation and cancer bowel disease. Several mouse models of colitis and associated cancer were used to analyse Hakai expression by immunohistochemistry. We also analysed Hakai expression in patients with inflamed colon biopsies from ulcerative colitis and Crohn's disease. By Hakai interactome analysis, it was identified Fatty Acid Synthase (FASN) as a novel Hakai-interacting protein. Moreover, we show that Hakai induces FASN ubiquitination and degradation via lysosome, thus regulating FASN-mediated lipid accumulation. An inverse expression of FASN and Hakai was detected in inflammatory AOM/DSS mouse model. In conclusion, Hakai regulates FASN ubiquitination and degradation, resulting in the regulation of FASN-mediated lipid accumulation, which is associated to the development of inflammatory bowel disease. The interaction between Hakai and FASN may be an important mechanism for the homeostasis of intestinal barrier function and in the pathogenesis of this disease. Nature Publishing Group UK 2022-10-20 /pmc/articles/PMC9584894/ /pubmed/36266428 http://dx.doi.org/10.1038/s41598-022-22295-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Roca-Lema, Daniel Quiroga, Macarena Khare, Vineeta Díaz-Díaz, Andrea Barreiro-Alonso, Aida Rodríguez-Alonso, Andrea Concha, Ángel Romay, Gabriela Cerdán, M. Esperanza Gasche, Christoph Figueroa, Angélica Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title | Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title_full | Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title_fullStr | Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title_full_unstemmed | Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title_short | Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease |
title_sort | role of the e3 ubiquitin-ligase hakai in intestinal inflammation and cancer bowel disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584894/ https://www.ncbi.nlm.nih.gov/pubmed/36266428 http://dx.doi.org/10.1038/s41598-022-22295-w |
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