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Fig. 1 | Cancer & Metabolism

Fig. 1

From: Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy

Fig. 1

GOT1 dependence exhibits tissue specificity. a Schematic of the GOT1 pathway in PDA. b Colony number after dox treatment in PDA (red) and CRC (blue) cell lines expressing dox-inducible (iDox) shRNAs against GOT1 (two independent hairpins; shGOT1 #1, shGOT1 #3) relative to a non-targeting hairpin (shNT). Error bars represent s.d. from biological replicates (n = 3). Mutations in KRAS, BRAF, and TP53 are presented in the table below the bar graph. WT, wild type; SM, silent mutation. c Western blots (left) and quantification (right) for GOT1 and vinculin (VCL) loading control from iDox-shGOT1 #1 PDA and CRC tumors. d, e Tumor growth curves and f, g final tumor weights from subcutaneous PDA xenografts (n = 8, BxPC-3 +/−dox tumors; n = 6, PA-TU-8902 +/−dox tumors). Error bars represent s.d. h, i Tumor growth curves and j, k final tumor weights from subcutaneous CRC xenografts (n = 5, DLD-1 +/−dox, HCT 116 +dox tumors; n = 4, HCT 116 −dox tumors). Error bars represent s.d. Tumor growth curves for the corresponding iDox-shNT lines are presented in Additional file 1: Figure S2b. l Western blot (left) and quantification (right) for GOT1 pathway components from a in wild-type PDA and CRC cell lines. AcCoA, acetyl-CoA; αKG, alpha-ketoglutarate; Asp, aspartate; Cit, citrate; Fum, fumarate; Glu, glutamate; GOT1, glutamate oxaloacetate transaminase 1; GOT2, glutamate oxaloacetate transaminase 2; Iso, isocitrate; Mal, malate; MDH1, malate dehydrogenase 1; ME1, malic enzyme 1; NADP+, oxidized nicotinamide adenine dinucleotide phosphate; NADPH, reduced nicotinamide adenine dinucleotide phosphate; OAA, oxaloacetate; Pyr, pyruvate; Suc, succinate. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; Student’s t test (unpaired, two-tailed)

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