Stress-induced eIF2α phosphorylation promotes tumor metastasis in oral squamous cell carcinoma

Stress granules (SGs) are non-membranous protein–RNA aggregates that form in the cytoplasm of mammalian cells under various stress conditions. In normal cells, SGs mitigate stress-induced damage by arresting translation. SGs have also been implicated in cancer cell tumor progression and metastasis through their interaction with key signaling pathways. However, their role in oral squamous cell carcinoma (OSCC) remains poorly understood, despite growing interest. In this study, we investigated SG formation and its regulatory effects on tumor progression and metastasis in OSCC. SG markers, including G3BP1, eIF2α, TIAR, and PABP, were significantly overexpressed in OSCC tissues compared with those in adjacent normal tissues. In mouse models established using OSCC cells subjected to hypoxia preconditioning or ISRIB treatment after sodium arsenite-induced stress, suppression of eIF2α phosphorylation was associated with reduced SG formation, tumor growth, and metastatic burden. Moreover, SG formation was elevated during hypoxia-induced stress, highlighting a stress-responsive regulatory mechanism. These findings indicate that SGs promote OSCC progression via eIF2α phosphorylation and might serve as a novel therapeutic target.