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GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity
GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement o...
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/PMC8748819/ https://www.ncbi.nlm.nih.gov/pubmed/35013389 http://dx.doi.org/10.1038/s41598-021-03787-7 |
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author | Rubbino, Federica Garlatti, Valentina Garzarelli, Valeria Massimino, Luca Spanò, Salvatore Iadarola, Paolo Cagnone, Maddalena Giera, Martin Heijink, Marieke Guglielmetti, Simone Arena, Vincenzo Malesci, Alberto Laghi, Luigi Danese, Silvio Vetrano, Stefania |
author_facet | Rubbino, Federica Garlatti, Valentina Garzarelli, Valeria Massimino, Luca Spanò, Salvatore Iadarola, Paolo Cagnone, Maddalena Giera, Martin Heijink, Marieke Guglielmetti, Simone Arena, Vincenzo Malesci, Alberto Laghi, Luigi Danese, Silvio Vetrano, Stefania |
author_sort | Rubbino, Federica |
collection | PubMed |
description | GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention. |
format | Online Article Text |
id | pubmed-8748819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87488192022-01-11 GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity Rubbino, Federica Garlatti, Valentina Garzarelli, Valeria Massimino, Luca Spanò, Salvatore Iadarola, Paolo Cagnone, Maddalena Giera, Martin Heijink, Marieke Guglielmetti, Simone Arena, Vincenzo Malesci, Alberto Laghi, Luigi Danese, Silvio Vetrano, Stefania Sci Rep Article GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention. Nature Publishing Group UK 2022-01-10 /pmc/articles/PMC8748819/ /pubmed/35013389 http://dx.doi.org/10.1038/s41598-021-03787-7 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 Rubbino, Federica Garlatti, Valentina Garzarelli, Valeria Massimino, Luca Spanò, Salvatore Iadarola, Paolo Cagnone, Maddalena Giera, Martin Heijink, Marieke Guglielmetti, Simone Arena, Vincenzo Malesci, Alberto Laghi, Luigi Danese, Silvio Vetrano, Stefania GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title | GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title_full | GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title_fullStr | GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title_full_unstemmed | GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title_short | GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
title_sort | gpr120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748819/ https://www.ncbi.nlm.nih.gov/pubmed/35013389 http://dx.doi.org/10.1038/s41598-021-03787-7 |
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