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Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis

Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, se...

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Autores principales: Matsushita, Makoto, Fujita, Kazutoshi, Hatano, Koji, De Velasco, Marco A., Uemura, Hirotsugu, Nonomura, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965097/
https://www.ncbi.nlm.nih.gov/pubmed/35370981
http://dx.doi.org/10.3389/fendo.2022.852382
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author Matsushita, Makoto
Fujita, Kazutoshi
Hatano, Koji
De Velasco, Marco A.
Uemura, Hirotsugu
Nonomura, Norio
author_facet Matsushita, Makoto
Fujita, Kazutoshi
Hatano, Koji
De Velasco, Marco A.
Uemura, Hirotsugu
Nonomura, Norio
author_sort Matsushita, Makoto
collection PubMed
description Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa. Because the IGF-1 receptor is overexpressed in PCa, IGF-1 can accelerate PCa growth by activating phosphoinositide 3-kinase and mitogen-activated protein kinase, or increasing sex hormone sensitivity. Short-chain fatty acids (SCFAs) are beneficial gut microbial metabolites, mainly because of their anti-inflammatory effects. However, we have demonstrated that gut microbiota-derived SCFAs increase the production of IGF-1 in the liver and prostate. This promotes the progression of PCa by the activation of IGF-1 receptor downstream signaling. In addition, the relative abundance of SCFA-producing bacteria, such as Alistipes, are increased in gut microbiomes of patients with high-grade PCa. IGF-1 production is therefore affected by the gut microbiome, dietary habits, and genetic background, and may play a central role in prostate carcinogenesis. The pro-tumor effects of bacteria and diet-derived metabolites might be potentially countered through dietary regimens and supplements. The specific diets or supplements that are effective are unclear. Further research into the “Gut–IGF-1–Prostate Axis” may help discover optimal diets and nutritional supplements that could be implemented for prevention of PCa.
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spelling pubmed-89650972022-03-31 Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis Matsushita, Makoto Fujita, Kazutoshi Hatano, Koji De Velasco, Marco A. Uemura, Hirotsugu Nonomura, Norio Front Endocrinol (Lausanne) Endocrinology Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa. Because the IGF-1 receptor is overexpressed in PCa, IGF-1 can accelerate PCa growth by activating phosphoinositide 3-kinase and mitogen-activated protein kinase, or increasing sex hormone sensitivity. Short-chain fatty acids (SCFAs) are beneficial gut microbial metabolites, mainly because of their anti-inflammatory effects. However, we have demonstrated that gut microbiota-derived SCFAs increase the production of IGF-1 in the liver and prostate. This promotes the progression of PCa by the activation of IGF-1 receptor downstream signaling. In addition, the relative abundance of SCFA-producing bacteria, such as Alistipes, are increased in gut microbiomes of patients with high-grade PCa. IGF-1 production is therefore affected by the gut microbiome, dietary habits, and genetic background, and may play a central role in prostate carcinogenesis. The pro-tumor effects of bacteria and diet-derived metabolites might be potentially countered through dietary regimens and supplements. The specific diets or supplements that are effective are unclear. Further research into the “Gut–IGF-1–Prostate Axis” may help discover optimal diets and nutritional supplements that could be implemented for prevention of PCa. Frontiers Media S.A. 2022-03-15 /pmc/articles/PMC8965097/ /pubmed/35370981 http://dx.doi.org/10.3389/fendo.2022.852382 Text en Copyright © 2022 Matsushita, Fujita, Hatano, De Velasco, Uemura and Nonomura https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Endocrinology
Matsushita, Makoto
Fujita, Kazutoshi
Hatano, Koji
De Velasco, Marco A.
Uemura, Hirotsugu
Nonomura, Norio
Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title_full Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title_fullStr Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title_full_unstemmed Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title_short Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis
title_sort connecting the dots between the gut–igf-1–prostate axis: a role of igf-1 in prostate carcinogenesis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965097/
https://www.ncbi.nlm.nih.gov/pubmed/35370981
http://dx.doi.org/10.3389/fendo.2022.852382
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