FMRP as a Key Regulator of Stress Granule Dynamics in Cholangiocarcinoma and Melanoma Cells

Stress granules (SGs) are dynamic, phase-dense cytosolic particles whose properties are dominated by weak interactions between proteins and RNAs. They form in response to cellular stress and play a critical role in regulating mRNA metabolism and cell survival. The Fragile X Messenger Ribonucleoprotein 1 (FMRP), a multifunctional RNA-binding protein mutated or absent in Fragile X Syndrome, has recently emerged as a key player in SG biology and cancer progression. In this study, we investigate the role of FMRP in SG assembly in liver and melanoma cancer cells exposed to oxidative stress induced by sodium arsenite. We demonstrate that FMRP co-localizes with the SG marker G3BP1 and is essential for its stability and cytoplasmic localization. Depletion of FMRP leads to a significant reduction in G3BP1 expression, impaired SG formation, and increased cellular sensitivity to stress. Furthermore, FMRP interacts with other SG components, including TIA-1, and modulates the organization of SGs without affecting TIA-1 expression. Our findings highlight FMRP as a central regulator of SG dynamics and suggest that targeting the FMRP–G3BP1 axis may offer novel therapeutic opportunities in aggressive and treatment-resistant cancers.