The Dual Role of Serotonin in Colorectal Cancer

结直肠癌 血清素 医学 生物 5-羟色胺能 免疫系统 内科学 癌变 平衡 癌症研究 大肠癌小鼠模型的建立 神经科学 癌症 内分泌学 免疫学 受体
作者
Vinicius Kannen,Michael Bäder,Juliana Yumi Sakita,Sérgio Akira Uyemura,Jeremy A. Squire
出处
期刊:Trends in Endocrinology and Metabolism [Elsevier]
卷期号:31 (8): 611-625 被引量:37
标识
DOI:10.1016/j.tem.2020.04.008
摘要

Both brain and peripheral cells can synthesize 5-HT from the essential amino acid tryptophan, although intestinal enteroendocrine cells produce the most substantial amount of this hormone in the human body. The serotonergic system encompasses a range of elements required for its synthesis, storage, release, transport, signaling, and degradation, from which it modulates essential functions in keeping with the body homeostasis. Genetic, behavioral, or environmental factors may deregulate the serotonergic system functions, promoting a significant number of pathological conditions. This has been expanded to include different types of cancer. A deregulated serotonergic system may be related to the development of colorectal cancer, because it can either promote or inhibit tumorigenesis in the colon through a combined modulation of DNA repair mechanisms and immune response. Serotonin (5-HT) has complex effects on the central nervous system (CNS), neuroendocrine mechanisms, immunological reactions, intestinal microbiome, and cancer. It has been associated with more severe signs and symptoms of colitis, as well as promoting colorectal cancer (CRC) cells toward expansion. However, recent findings revealed that impairments in 5-HT synthesis lead to high levels of DNA damage in colonocytes, which is linked with inflammatory reactions promoting the development of CRC. Here, we review the diverse roles of 5-HT in intestinal homeostasis and in CRC and discuss how improved understanding of the modulation of the 5-HT pathway could be helpful for the design of novel anticancer therapies. Serotonin (5-HT) has complex effects on the central nervous system (CNS), neuroendocrine mechanisms, immunological reactions, intestinal microbiome, and cancer. It has been associated with more severe signs and symptoms of colitis, as well as promoting colorectal cancer (CRC) cells toward expansion. However, recent findings revealed that impairments in 5-HT synthesis lead to high levels of DNA damage in colonocytes, which is linked with inflammatory reactions promoting the development of CRC. Here, we review the diverse roles of 5-HT in intestinal homeostasis and in CRC and discuss how improved understanding of the modulation of the 5-HT pathway could be helpful for the design of novel anticancer therapies.
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