Extended Data Fig. 4: Influence of SPT and PHGDH inhibition on sphingolipid metabolism.
From: Serine restriction alters sphingolipid diversity to constrain tumour growth
a–d, Abundances of deoxyDHCER (a), deoxyCER (b), DHCER (c) and CER (d) in HCT116 xenograft tumours from mice fed an −SG diet and administered vehicle, 0.03 mg/kg myriocin or 0.3 mg/kg myriocin (n = 16 for each treatment). e–h, Abundances of deoxyDHCER (e), deoxyCER (f), DHCER (g) and CER (h) in livers from HCT116 xenograft-bearing mice fed an −SG diet and administered vehicle (n = 8 for e, f, h and n = 7 for g), 0.03 mg/kg myriocin (n = 8) or 0.3 mg/kg myriocin (n = 8). i, Weight loss in mice after tumour inoculation in mice administered vehicle (n = 7), 0.03 mg/kg myriocin (n = 8) or 0.3 mg/kg myriocin (n = 8). j, Schematic describing in vivo sphingolipid physiology under high- and low-dose myriocin treatments generated using BioRender. k, Fractional labelling of serine (1 − M0) from HCT116 spheroids cultured with [U-13C6]glucose for 24 h and treated with vehicle or 5 μM PH-755 (n = 3 culture wells for each). l, HCT116 spheroid growth in medium containing 0.4 mM or 1.0 mM serine and treated with vehicle or 5 μM PH-755 (n = 3 culture wells for each). m, Total deoxysphinganine abundances in HCT116 spheroids grown for 5 d in medium with 0.4 mM or 1 mM serine, and treated with vehicle or 5 μM PH-755 (n = 3 culture wells for each). n, Total deoxysphinganine abundances in A549, HCT116 and MCF7 spheroids treated with vehicle or 5 μM PH-755 (n = 3 culture wells each). o, Plasma serine, glycine and alanine in mice treated with vehicle or PH-755 (n = 7 each). Two-way ANOVA (a–h, k–n), one-way ANOVA (i), or two-sided Student’s t-test (o) was performed, with no adjustment for multiple comparison. Similar results were obtained in two independent experiments (k–n). Data are mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.0001 or #P < 0.0001.
