GPR120 Prevents Colorectal Adenocarcinoma Progression by Sustaining The Mucosal Barrier Integrity
| Autor: | Simone Guglielmetti, Stefania Vetrano, Silvio Danese, M. Giera, Marieke Heijink, Federica Rubbino, Luigi Laghi, Valentina Garlatti, V. Arena, Salvatore Spanò, Luca Massimino, Valeria Garzarelli, Paolo Iadarola, A. Malesci, Maddalena Cagnone |
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| Rok vydání: | 2021 |
| Předmět: |
Cell biology
Molecular biology Colon Science Adenocarcinoma Microbiology Article Permeability Receptors G-Protein-Coupled Text mining Animals Humans Barrier integrity Medicine Colorectal adenocarcinoma Intestinal Mucosa Cancer Cell Proliferation Mice Knockout Multidisciplinary business.industry Gastroenterology GPR120 Gastrointestinal Microbiome Tumor Burden Bacterial Translocation Disease Progression Cancer research Dysbiosis Colitis-Associated Neoplasms business |
| Zdroj: | Scientific Reports, 12(1). NATURE PORTFOLIO Scientific Reports Scientific Reports, Vol 12, Iss 1, Pp 1-18 (2022) |
| DOI: | 10.21203/rs.3.rs-598555/v1 |
| Popis: | Background&Aims: GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 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. Methods: 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. Results: Our work for the first time highlight 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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