Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.
Environ Pollut. 2024 Dec 1;362:124997. doi: 10.1016/j.envpol.2024.124997. Epub 2024 Sep 19.
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.
应激颗粒（SGs）是一种无膜的动态细胞器，影响包括细胞存活、增殖和恶性转化在内的多种细胞途径。六价铬[Cr(VI)]是一种与严重环境健康风险相关的有毒重金属。据报道，低水平的环境暴露于 Cr(VI)会导致癌症，但 SGs 在 Cr(VI)诱导的健康影响中的作用尚不清楚。本研究旨在阐明 Cr(VI)暴露对 SG 动力学的影响以及 SGs 在 Cr(VI)诱导的恶性转化中的作用。结果表明，急性暴露于高浓度 Cr(VI)和长期暴露于低浓度 Cr(VI)均可诱导人支气管上皮 BEAS-2B 细胞中 SG 的形成。与未经预暴露的细胞相比，预先暴露于 Cr(VI)的细胞表现出更强的 SG 反应。在长达 12 个月的时间内，持续暴露于低浓度 Cr(VI)的细胞中 SG 反应上调与恶性特性增加有关，包括增殖率、球体形成和恶性标志物。敲除 Cr(VI)转化（CrT）细胞中的 SG 核心蛋白 G3BP1 可减少 SG 形成和恶性特性，包括增殖率、球体形成和恶性标志物。结果支持 SGs 在介导 Cr(VI)诱导的恶性转化中发挥关键作用，这是一种依赖于 G3BP1 的方式，代表了一种新的机制和潜在的治疗靶点。
