2. Academic Validation
  3. Transglutaminase 2 nuclear localization enhances glioblastoma radiation resistance

Transglutaminase 2 nuclear localization enhances glioblastoma radiation resistance

  • Discov Oncol. 2025 May 30;16(1):952. doi: 10.1007/s12672-025-02599-9.
Cuiping Sun 1 2 3,  Zhiyong Du 1 2,  Wenhui Yang 1 2 3,  Qing Wang 4 5 6
Affiliations

Affiliations

  • 1 Neuroscience Center, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
  • 2 Laboratory, Wuxi Neurosurgical Institute, Wuxi, 214002, China.
  • 3 Neurological Medicine Research Centre, Jiangnan University, Wuxi, 214122, China.
  • 4 Neuroscience Center, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China. wxwqnj@126.com.
  • 5 Laboratory, Wuxi Neurosurgical Institute, Wuxi, 214002, China. wxwqnj@126.com.
  • 6 Department of Neurosurgery, Wuxi No.2 People's Hospital (Jiangnan University Medical Center), No. 585 Xingyuan North Road, Liangxi District, Wuxi, 214002, China. wxwqnj@126.com.
PMID: 40445445 DOI: 10.1007/s12672-025-02599-9
Abstract

Radiotherapy remains the cornerstone of treatment for glioblastoma (GBM). However, the frequent occurrence of radiation resistance presents a significant therapeutic challenge. A comprehensive understanding of the mechanisms underlying this resistance is essential for improving GBM treatment strategies. In the present study, live-dead cell staining and immunofluorescence staining were employed, and irradiation-resistant cell lines were established. It was observed that Transglutaminase 2 (TGM2) plays a pivotal role in enhancing radiation resistance in GBM, facilitating cell proliferation, and promoting DNA damage repair following irradiation. Moreover, immunofluorescence and nucleoplasmic protein extraction assays revealed that TGM2 in GBM rapidly translocates into the nucleus upon irradiation. Through co-immunoprecipitation assays, TGM2 was identified as binding to an increased amount of p53 proteins, thereby promoting p53 degradation post-irradiation. Notably, inhibition of this interaction resulted in a reduction of radiation resistance in GBM. In summary, this study underscores the significance of TGM2 nuclear translocation in radiation resistance and suggests that disrupting TGM2 binding to p53 may offer novel therapeutic insights for overcoming radiation resistance in GBM.

Keywords

DNA damage repair; Glioblastoma; Radiation resistance; Transglutaminase 2; Translocation; p53.

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