Extended Data Fig. 4: BCAT2-mediated BCAA catabolism is essential for PDAC.
From: BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma
a, Establishment of PANC1 cells with stable BCAT2 knockdown (data are representative of three biologically independent experiments). b-h, Quantification of metabolites abundance in SW1990 (b, e, f, mean ± s.e.m. of n = 3 biologically independent experiments, two-tailed t-test) and PANC1 (c, e, g, mean ± s.e.m. of n = 3 biologically independent experiments, two-tailed t-test) cells with or without BCAT2 silencing and pancreatic duct organoids from KC or KC;Bcat2-/- mice (d,e,h, mean ± s.e.m. of n = 4 biologically independent experiments (d, h), n = 3 biologically independent experiments (e), two-tailed t-test). i. Establishment of BCAT2 WT or Y229A put back in SW1990 cells. Data are representative of three biologically independent experiments. j-n, BCAT2 WT but not Y229A put back recovers mitochondrial potential (j, mean ± s.e.m. of n = 3 biologically independent experiments, two-tailed t-test), mitochondrial ROS (k, mean ± s.e.m. of n = 5 biologically independent experiments, two-tailed t-test), OCR (l, mean ± s.e.m. of n = 6 biologically independent experiments, two-tailed t-test), ECAR (m, mean ± s.e.m. of n = 6 biologically independent experiments, two-tailed t-test) and cell proliferation (n, mean ± s.e.m. of n = 4 biologically independent experiments, ***p < 0.001, n.s. donates for no significance, detailed p value is available in Supplementary Table 3, two-tailed t-test). o, Establishment of KRASG12V-overexpressing H6C7 cells and KRAS-silencing PANC1 cells (data are representative of three biologically independent experiments). p, q, KC mice pancreatic ductal organoids growth in presence of BCAT2 inhibitors (20 μM, dissolved in DMSO) in combination with NBs (nucleobases, 250 μM, dissolved in DMSO) and BCKA (150 μM) (p) or BCAA at different concentrations (q) (each 4 fields, scale bar: 200 μm).
