Kim Jayoung, Yeon Austin, Kim Woong-Ki, Kim Khae-Hawn, Ohn Takbum
Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Cancer Sci Clin Ther. 2021;5(4):434-447. doi: 10.26502/jcsct.5079129. Epub 2021 Oct 15.
Stress granules (SGs) are cytoplasmic aggregates to reprogram gene expression in response to cellular stimulus. Here, we show that while SGs are being assembled in response to clotrimazole, an antifungal medication heterogeneous nuclear ribonucleoprotein (hnRNP) K, an RNA-binding protein that mediates translational silencing of mRNAs, is rapidly accumulated in SGs in U-2OS osteosarcoma cells. Forced expression of hnRNP K induces resistance to clotrimazole-induced apoptosis. Erk/MAPK is transiently activated in response to clotrimazole, and pharmacological suppression of the Erk/MAPK pathway sensitizes the cells to apoptosis. Inhibition of the Erk/MAPK pathway promotes the assembly of SGs. These results suggest that dynamic cytoplasmic formation of SGs and hnRNP K relocation to SGs may be defensive mechanisms against clotrimazole-induced apoptosis in U-2OS osteosarcoma cells.
应激颗粒（SGs）是细胞质聚集体，可响应细胞刺激重新编程基因表达。在此，我们表明，在抗真菌药物克霉唑刺激下组装SGs时，异质性核糖核蛋白（hnRNP）K（一种介导mRNA翻译沉默的RNA结合蛋白）在U-2OS骨肉瘤细胞的SGs中迅速积累。hnRNP K的强制表达诱导对克霉唑诱导的细胞凋亡产生抗性。Erk/MAPK在响应克霉唑时被短暂激活，并且对Erk/MAPK途径的药理学抑制使细胞对细胞凋亡敏感。抑制Erk/MAPK途径促进SGs的组装。这些结果表明，SGs的动态细胞质形成和hnRNP K向SGs的重新定位可能是U-2OS骨肉瘤细胞中对抗克霉唑诱导的细胞凋亡的防御机制。
