Fig. 4
From: Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy
GOT1 inhibition disrupts nucleotide metabolism in PDA. a Fold-change versus P value is plotted per metabolite as the average from three iDox-shGOT1 #1 PDA lines (+dox/−dox) over the average from three iDox-shGOT1 #1 CRC lines (+dox/−dox). Metabolites with filled circles were used for the pathway analysis in Additional file 1: Figure S6a. Metabolites identity is indicated for those with P < 0.05 and fold change +/−2. b Relative nucleic acid pools as determined by LC/MS in iDox-shGOT1 #1 PDA and CRC, presented as GOT1 knockdown over mock (+dox/−dox). c Relative IC50 of gemcitabine, 5-fluorouracil (5-FU), and oxaliplatin in iDox-shGOT1 #1 PDA and CRC cells upon GOT1 knockdown. The dose response curves from which the IC50s were derived are presented in Additional file 1: Figure S7e. ADP, adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; CDP, cytidine diphosphate; CMP, cytidine monophosphate; CTP, cytidine triphosphate; dAMP, deoxyadenosine monophosphate; dATP, deoxyadenosine triphosphate; dCDP, deoxycytidine diphosphate; dCMP, deoxycytidine monophosphate; dCTP, deoxycytidine triphosphate; dGDP, deoxyguanosine diphosphate; dGMP, deoxyguanosine monophosphate; dGTP, deoxyguanosine triphosphate; dTDP, deoxythymidine diphosphate; dTMP, deoxythymidine monophosphate; dTTP, deoxythymidine triphosphate; dUMP, deoxyuridine monophosphate; GDP, guanosine diphosphate; GMP, guanosine monophosphate; GTP, guanosine triphosphate; IDP, inosine diphosphate; IMP, inosine monophosphate; UDP, uridine diphosphate; UMP, uridine monophosphate; UTP, uridine triphosphate; XMP, xanthosine monophosphate. Error bars in b and c represent s.d. from biological replicates (n = 3). n.s., not significant; *P < 0.05; **P < 0.01; Student t test (unpaired, two-tailed)