Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications

Abstract

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.