Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2020; 26(35): 5223-5247
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5223
Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications
Noémie Legrand, Dan A Dixon, Cyril Sobolewski
Noémie Legrand, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva CH-1211, Switzerland
Dan A Dixon, Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, and University of Kansas Cancer Center, Lawrence, KS 66045, United States
Cyril Sobolewski, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva CH-1211, Switzerland
Author contributions: Sobolewski C, Legrand N, Dixon DA contributed to the writing of the manuscript; Sobolewski C contributed to the supervision of the manuscript; Dixon DA performed the critical revision of the manuscript for important intellectual content; all authors critically revised the manuscript and approved the final version for publication.
Supported by Geneva Cancer League, No. 1711; National Institutes of Health, No. R01 CA243445; and National Cancer Institute Cancer Center Support Grant, No. P30 CA168524.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Cyril Sobolewski, PhD, Research Associate, Senior Scientist, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CMU, 1 rue Michel-Servet, Geneva CH-1211, Switzerland.
Received: July 22, 2020
Peer-review started: July 22, 2020
First decision: August 8, 2020
Revised: August 12, 2020
Accepted: September 3, 2020
Article in press: September 3, 2020
Published online: September 21, 2020

Stress granules (SGs) represent important non-membrane cytoplasmic compartments, involved in cellular adaptation to various stressful conditions (e.g., hypoxia, nutrient deprivation, oxidative stress). These granules contain several scaffold proteins and RNA-binding proteins, which bind to mRNAs and keep them translationally silent while protecting them from harmful conditions. Although the role of SGs in cancer development is still poorly known and vary between cancer types, increasing evidence indicate that the expression and/or the activity of several key SGs components are deregulated in colorectal tumors but also in pre-neoplastic conditions (e.g., inflammatory bowel disease), thus suggesting a potential role in the onset of colorectal cancer (CRC). It is therefore believed that SGs formation importantly contributes to various steps of colorectal tumorigenesis but also in chemoresistance. As CRC is the third most frequent cancer and one of the leading causes of cancer mortality worldwide, development of new therapeutic targets is needed to offset the development of chemoresistance and formation of metastasis. Abolishing SGs assembly may therefore represent an appealing therapeutic strategy to re-sensitize colon cancer cells to anti-cancer chemotherapies. In this review, we summarize the current knowledge on SGs in colorectal cancer and the potential therapeutic strategies that could be employed to target them.

Keywords: Stress-Granules, Colorectal cancer, Adenylate-Uridylate-rich element-binding proteins, Post-transcriptional regulation, Oncogenes, Tumor suppressors

Core Tip: Colorectal cancer (CRC) represent the second cause of cancer mortality worldwide. Although changes in genetic landscape associated with CRC development have been identified, most frequent mutations are currently undruggable. The development of chemoresistance represent a major cause of CRC-associated mortality and identifying mechanisms allowing cancer cells to avoid these treatments may considerably improve clinical outcomes. Current findings indicate that cancers cells can preserve their expressed mRNAs in harmful conditions by storing them in small cytoplasmic granules, called Stress granules (SGs), where they are kept translationally silent. Targeting these SGs proteins may therefore represent a novel and efficient therapeutic approach.