Stress granules play a critical role in hexavalent chromium-induced malignancy in a G3BP1 dependent manner

Stress granules (SGs) are dynamic membraneless organelles influencing multiple cellular pathways including cell survival, proliferation, and malignancy. Hexavalent chromium [Cr(VI)] is a toxic heavy metal associated with severe environmental health risks. Low-level environmental exposure to Cr(VI) has been reported to cause cancer, but the role of SGs in Cr(VI)-induced health effects remains unclear. This study was intended to elucidate the impact of Cr(VI) exposure on SG dynamics and the role of SGs in Cr(VI)-induced malignancy. Results showed that both acute exposure to high concentration of Cr(VI) and prolonged exposure to low concentration of Cr(VI)-induced SG formation in human bronchial epithelium BEAS-2B cells. Cells pre-exposed to Cr(VI) exhibited a more robust SG response compared to cells without pre-exposure. An up-regulated SG response was associated with increased malignant properties in cells exposed to low concentration Cr(VI) for an extended period of time up to 12 months. Knocking out the SG core protein G3BP1 in Cr(VI)-transformed (CrT) cells reduced SG formation and malignant properties, including proliferation rate, sphere formation, and malignant markers. The results support a critical role for SGs in mediating Cr(VI)-induced malignancy in a G3BP1-dependent manner, representing a novel mechanism and a potential therapeutic target.