Integrated genetic and metabolic landscapes predict vulnerabilities of temozolomide resistant glioblastoma cells.

ABSTRACT: Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, malate aspartate shunt, and oxidativ

SUBMITTER: Immanuel SRC 

PROVIDER: S-EPMC7794364 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature