Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines

• DOI: 10.1007/s11306-020-01674-2
• Publication Date: 2020-04-16T05:02:53Z
• Authors: Dorna Varshavi; Dorsa Varshavi; Nicola McCarthy; Kirill Veselkov; Hector C. Keun; Jeremy R. Everett
• Keywords: Viral Oncogene

Abstract Introduction Kirsten Rat Sarcoma Viral Oncogene Homolog ( KRAS ) mutations occur in approximately one-third of colorectal (CRC) tumours and have been associated with poor prognosis resistance to some therapeutics. In addition the well-documented pro-tumorigenic role mutant Ras alleles, there is evidence suggesting that not all are equal position type amino acid substitutions regulate biochemical activity transforming capacity mutations. Objectives To investigate metabolic signatures different codons 12, 13, 61 146 determine what pathways affected by Methods We applied an NMR-based metabonomics approach compare profiles intracellular extracts extracellular media from isogenic human SW48 CRC cell lines 12 (G12D, G12A, G12C, G12S, G12R, G12V), 13 (G13D), Q61H A146T their wild-type counterpart. used false discovery rate (FDR)-corrected analysis variance (ANOVA) metabolites were statistically significantly concentration between mutants. Results cells carrying distinct exhibited differential remodelling, including differences glycolysis, glutamine utilization acid, nucleotide hexosamine metabolism. Conclusions Metabolic among might play a responses anticancer treatments hence could be exploited as novel vulnerabilities develop more effective therapies against oncogenic KRAS.