Phosphoglycerate mutase 1 (PGAM1) overexpression promotes radio- and chemoresistance in gliomas by activating the DNA damage response

Tor-Christian Aase Johannessen; Joydeep Mukherjee

doi:10.1080/23723556.2021.1875804

Phosphoglycerate mutase 1 (PGAM1) overexpression promotes radio- and chemoresistance in gliomas by activating the DNA damage response

Mol Cell Oncol. 2021 Mar 22;8(2):1875804. doi: 10.1080/23723556.2021.1875804. eCollection 2021.

Authors

Tor-Christian Aase Johannessen^{1

2}, Joydeep Mukherjee²

Affiliations

¹ Department of Oncology, Haukeland University Hospital, Bergen, Norway.
² Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.

Abstract

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.

Keywords: DNA damage repair; Glioma; IR; PGAM1; TMZ; WIP1; treatment resistance.