Phase separation orchestrates cancer signaling: Stress granules as a promising target for cancer therapy

R Sugiura, R Satoh, N Tomimoto, T Takasaki - Phase Separation in Living …, 2023 - Springer
Phase Separation in Living Cells: Benefits and Risks, 2023Springer
Liquid–liquid phase separation (LLPS) has recently emerged as a new fundamental
mechanism for the eukaryotic cellular organization via the formation of membrane-less
intracellular organelles exemplified by nucleoli, P-bodies, and stress granules
(SGs)(Mahboubi and Stochaj; Luo et al.; Molliex et al.). These membrane-less condensates
play important roles in various physiological and pathological processes, including
regulation of gene expression, cellular stress responses, and signal transduction. Recent …
Abstract
Liquid–liquid phase separation (LLPS) has recently emerged as a new fundamental mechanism for the eukaryotic cellular organization via the formation of membrane-less intracellular organelles exemplified by nucleoli, P-bodies, and stress granules (SGs) (Mahboubi and Stochaj ; Luo et al. ; Molliex et al. ). These membrane-less condensates play important roles in various physiological and pathological processes, including regulation of gene expression, cellular stress responses, and signal transduction. Recent studies have highlighted the importance of these biomolecular condensates in tumorigenesis. Among them, SGs have attracted strong attention as a promising target for cancer treatment because of their involvement in various aspects of cancer progression, ranging from cancer formation to metastasis, as well as drug resistance. SGs regulate important cancer signaling pathways, such as mTOR and MAPK via spatial recruitment of signaling molecules thus indicating that SGs constitute signaling hubs that can rewire cancer signal transduction. Additionally, exciting discoveries in mammals as well as model organisms including yeasts have indicated that several molecules involved in cancer/proliferation signaling have been shown to upregulate SG formation. In this review, we summarize the fundamental aspects of SGs as a new paradigm for dynamic modulators of various cellular signal transduction systems and then focus on recent advances in our understanding of the role of SGs in cancer biology and its application for therapeutic strategies targeting SGs.
Springer
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