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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2019; 25(30): 4092-4104
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4092
G protein-coupled estrogen receptor in colon function, immune regulation and carcinogenesis
Damian Jacenik, Ellen J Beswick, Wanda M Krajewska, Eric R Prossnitz
Damian Jacenik, Wanda M Krajewska, Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz 90-236, Poland
Damian Jacenik, Eric R Prossnitz, Department of Internal Medicine, School of Medicine, and UNM Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM 87131, United States
Ellen J Beswick, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84132, United States
Author contributions: Jacenik D conceived of this paper and performed the literature review; all authors contributed to writing, critical revisions, editing and approval of the final manuscript.
Supported by grants from the National Science Centre, Poland (2017/24/T/NZ5/00045 and 2015/17/N/NZ5/00336 to Damian Jacenik), the U.S. National Institutes of Health (NIH R01 CA163890 and CA194496 to Eric R. Prossnitz; R01 CA207051 to Ellen J. Beswick), the UNM Comprehensive Cancer Center (P30 CA118100), the Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence (P20 GM121176) and Dialysis Clinic, Inc. (to Eric R. Prossnitz).
Conflict-of-interest statement: Dr. Prossnitz discloses US patents 7,875,721, 8,487,100 and 10,251,870 for GPER-selective compounds and their applications.
Open-Access: This article is an open-access article, which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Eric R Prossnitz, PhD, Distinguished Professor, Department of Internal Medicine, School of Medicine, and UNM Comprehensive Cancer Center, University of New Mexico, 2325 Camino de Salud, Albuquerque, NM 87131, United States. eprossnitz@salud.unm.edu
Telephone: +1-505-272-5647
Received: March 28, 2019
Peer-review started: March 28, 2019
First decision: May 24, 2019
Revised: July 3, 2019
Accepted: July 5, 2019
Article in press: July 5, 2019
Published online: August 14, 2019
Processing time: 139 Days and 20 Hours
Abstract

Estrogens play important roles in the development and progression of multiple tumor types. Accumulating evidence points to the significance of estrogen action not only in tumors of hormonally regulated tissues such as the breast, endometrium and ovary, but also in the development of colorectal cancer (CRC). The effects of estrogens in physiological and pathophysiological conditions are mediated by the nuclear estrogen receptors α and β, as well as the membrane-bound G protein-coupled estrogen receptor (GPER). The roles of GPER in CRC development and progression, however, remain poorly understood. Studies on the functions of GPER in the colon have shown that this estrogen receptor regulates colonic motility as well as immune responses in CRC-associated diseases, such as Crohn’s disease and ulcerative colitis. GPER is also involved in cell cycle regulation, endoplasmic reticulum stress, proliferation, apoptosis, vascularization, cell migration, and the regulation of fatty acid and estrogen metabolism in CRC cells. Thus, multiple lines of evidence suggest that GPER may play an important role in colorectal carcinogenesis. In this review, we present the current state of knowledge regarding the contribution of GPER to colon function and CRC.

Keywords: G protein-coupled estrogen receptor; Colorectal cancer; Proliferation; Migration; Colonic motility; Inflammatory bowel disease

Core tip: G protein-coupled estrogen receptor (GPER) is a membrane-bound estrogen receptor that participates in the rapid non-genomic actions of estrogens involving numerous downstream signaling pathways. GPER is expressed in the gastrointestinal tract and is engaged in physiological and pathophysiological processes in the colon. This review aims to assess the significance of GPER expression and estrogenic signaling in colorectal carcinogenesis.