Fig. 1: PDA requires GOT1 for cellular proliferation and tumor growth.
From: GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis
a Malate-aspartate shuttle model. b, c Colony formation and immunoblot analysis of Pa-Tu-8902 cells stably expressing iDox-shRNA constructs following 10 days GOT1 knockdown. shRNAs target the coding region of GOT1 (sh1), or the 3′UTR region of GOT1 (sh3). Parental (parent) and scramble (shNT) conditions are also displayed. Vinculin (VCL) was used as a loading control. Immunoblot shown in (c) is representative of three independent experiments. d Relative colony number across a panel of PDA cell lines, n = 3 biological replicates. e Subcutaneous xenograft tumors from three PDA cell lines. Treatment with dox (red) or vehicle (black) (BxPC-3 mock-treated n = 8 mice; dox n = 6 mice; ****P = < 0.0001, MIA PaCa-2 n = 6 mice each group; ****P < 0.0001, Pa-Tu-8902 n = 6 mice each group; ***P = 0.0008). f Orthotopic xenograft tumor growth from Pa-Tu-8902 iDox-shGOT1 stable cells expressing firefly luciferase (FLuc) n = 5 and n = 6 mice were used for vehicle and dox cohorts, respectively; *P = 0.0138, *P = 0.0165, **P = 0.0102. Data shown represent biological replicates examined over one experiment and reproduced in two independent experiments. Error bars represent mean ± SD. Source data are provided as a Source Data file. Gln glutamine, αKG alpha-ketoglutarate, Glu glutamate, OAA oxaloacetate, NADH nicotinamide adenine dinucleotide, NADPH nicotinamide adenine dinucleotide phosphate, GOT glutamic oxaloacetic transaminase, MDH malate dehydrogenase, ME malic enzyme.
