Phosphoglycerate mutase 1 (PGAM1) overexpression promotes radio- and chemoresistance in gliomas by activating the DNA damage response.
Tor-Christian Aase JohannessenJoydeep MukherjeePublished in: Molecular & cellular oncology (2021)
The glycolytic enzyme PGAM1 is overexpressed in gliomas where it efficiently facilitates the repair of DNA damage. Mechanistically, PGAM1 prevents inactivation of the ataxia-telangiectasia mutated (ATM) signaling pathway by sequestering the wild-type p53-induced phosphatase 1 (WIP1) in the cytoplasm. Genetic inhibition of PGAM1 expression subsequently sensitizes glioma cells against irradiation and chemotherapy-induced DNA damage.
Keyphrases
- dna damage
- dna damage response
- dna repair
- wild type
- signaling pathway
- chemotherapy induced
- high grade
- oxidative stress
- induced apoptosis
- poor prognosis
- diabetic rats
- high glucose
- pi k akt
- early onset
- genome wide
- epithelial mesenchymal transition
- transcription factor
- binding protein
- mouse model
- endothelial cells
- radiation therapy
- protein kinase