Extended Data Fig. 5: PA deprivation slows down mammary tumor growth in PDXs and WM tumors.
From: Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer
a, Selected metabolites from GC–MS analysis of 4T1 cells with and without PA as well as CoA rescue. b, Western blot analysis of 4T1 cells with and without PA and with increasing amounts of CoA as a rescue (representative image of 3 biological repeats). c, Mouse weight during PA deprivation in the PDX-cohort (control diet, n = 7; PA-free diet, n = 8; error bar represents s.d.) d, Growth of WMMix tumors from mice fed a PA-free or control diet (n = 5 tumors from independent animals; error bar represent s.d., P = 0.02401). e Proliferation of WMMix tumors with and without PA quantified as BrDU-positive cells over total cells (n = 4 tumors from independent biological replicates, one section per tumor; WMlow, P = 0.0304; WMhigh, P = 0.0126). f, Densitometric analysis of cleaved caspase 3 presence, normalised to actin in HCI002 tumors from mice fed PA-free or control diet (n = 5 tumor protein extracts from independent biological replicates, P = 0.00171). g-h, LC–MS analysis of WMMix tumors receiving a bolus of [13C6]glucose shows no significantly reduced amounts of free CoA-SH, Acetyl-CoA and labeled Acetyl-CoA isotopologues upon PA deprivation (n = 5 tumors from independent animals). i, Selected metabolites of LC–MS analysis of HCI002 tumors show widespread reduction in polar metabolite levels in tumors grown on PA-free diet. j, LC–MS analysis of HCI002 tumors receiving a bolus of [13C6]glucose shows widespread reduction in label incorporation in selected metabolites upon PA deprivation, but little difference in the fractional enrichment. k, LC–MS analysis of WMMix tumors shows widespread reduction in polar metabolite levels in tumors grown on PA-free diet. l, LC–MS analysis of WMMix tumors receiving a bolus of [13C6]glucose shows widespread reduction in label incorporation in selected metabolites upon PA deprivation, but little difference in the fractional enrichment. m, LC–MS analysis of the apolar fraction of HCI002 PDX tumors (n = 7 control, n = 8 PA-free) shows accumulation of triglycerides (TG), following PA deprivation (significance was calculated with a unpaired two-sided non-adjusted Student’s t-test). n, LC–MS analysis of the apolar fraction of WMMix tumors (n = 5 tumors from independent animals) shows accumulation of diglycerides (DG) and triglycerides (TG), following PA deprivation (significance was calculated with a unpaired two-sided non-adjusted Student’s t-test). All box and whisker plots represent the following: Line: median, box: IQR, whiskers: 1.5 x IQR limited by largest/smallest NEV. Significance was calculated with an unpaired two-tailed t-test. P value: *<0.05, ** 0.001. See also Fig. 4.
