Author:
Matsushita Makoto,Fujita Kazutoshi,Hatano Koji,De Velasco Marco A.,Uemura Hirotsugu,Nonomura Norio
Abstract
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.
Funder
Japan Society for the Promotion of Science
Subject
Endocrinology, Diabetes and Metabolism
Reference96 articles.
1. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;Bray;CA Cancer J Clin,2018
2. Prostate Cancer Racial, Socioeconomic, Geographic Disparities: Targeting the Genomic Landscape and Splicing Events in Search for Diagnostic, Prognostic and Therapeutic Targets;Marima;Am J Cancer Res,2021
3. Lifetime Risk of Being Diagnosed With, or Dying From, Prostate Cancer by Major Ethnic Group in England 2008-2010;Lloyd;BMC Med,2015
4. Geographic Pathology of Latent Prostatic Carcinoma;Yatani;Int J cancer,1982
5. Influence of Diet and Nutrition on Prostate Cancer;Matsushita;Int J Mol Sci,2020
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