PPM1G suppresses ferroptosis in lung squamous cell carcinoma by dephosphorylating and stabilizing GPX4

Previous studies have highlighted the role of PPM1G in driving the progression of multiple cancer types. However, its specific function in lung squamous cell carcinoma (LUSC) remains poorly understood. In this study, we employed cellular and animal models to systematically explore the involvement of PPM1G in LUSC progression. Our results revealed that PPM1G acts as an oncogene, exerting a significant promotional effect on key malignant behaviors of LUSC cells, including proliferation, migration, and invasion. In animal experiments, knockdown of PPM1G not only inhibited the in vivo proliferative capacity of LUSC but also enhanced its sensitivity to cisplatin-based chemotherapy regimens. Mechanistically, we found that PPM1G confers resistance to ferroptosis by regulating the phosphorylation and stability of GPX4, a critical regulator of lipid peroxidation and ferroptosis. These findings identify PPM1G as a promising therapeutic target of designing targeted drugs for treatment of LUSC.