MST1 enhances radio-sensitivity in glioblastoma by suppressing autophagy and promoting apoptosis.

Resistance to radiotherapy remains a significant challenge in the treatment of glioblastoma (GBM). However, the mechanism underlying radioresistance in GBM cells are not fully elucidated. Autophagy has been implicated in supporting cancer cell growth and contributing to therapeutic resistance. Mammalian Ste20-like kinase 1 (MST1) exhibits variable expression patterns across a range of neoplasms, yet its role in modulating GBM radiosensitivity remains unclear. Analysis of The Cancer Genome Atlas (TCGA) disclosed that the correlation between MST1 level and patient survival varied across different cancer types. Notably, MST1 expression was decreased in the majority of tumors examined, including GBM, compared with normal tissue. A radiation-resistant GBM cell line (U87-IR) was established through sequential irradiation and observed significant downregulation of MST1 in U87-IR cells. Overexpression of MST1 increased the production of radiation-induced reactive oxygen species (ROS), impaired mitochondrial function, and promoted apoptosis by suppressing autophagy. Collectively, these results suggest that reduced MST1 expression enhances the survival of radiation-exposed GBM cells. Overexpression of MST1 inhibits autophagy and promotes apoptosis, thus enhancing the radio-sensitivity of GBM.