Extended Data Fig. 12: LPC 18:1 enhances the proliferation of cancer cells.

(a-d) Relative cell number of indicated cell lines (n = 4-5 per dose) after treatment with different doses of BSA-LPC 18:1 for 4 days. (e) Quantitation of LPC 18:1 in the serum of C57 BL/6 mice after subcutaneous administration of one dose of 80 mg/kg LPC 18:1 (n = 4) or vehicle (n = 4). (f) Quantitation of LPC 18:1 in the serum of C57 BL/6 mice after 7-day administration of a control diet (n = 5), a control diet + 10% fructose water (n = 5), or a control diet + 10% fructose water + daily i.p. injection of 50 mg/kg PF-06835919 (n = 3). (g) Relative mRNA expression of LPCAT isoforms 1-4 in CaSki cells. (h) Western Blot analysis of LPCAT1 from CaSki cells 3 days after transfection with either LPCAT1 siRNA or scrambled control RNA. (i) Schematic overview of a mechanism by which fructose mediates tumour growth indirectly, by increasing the availability of fructose-derived nutrients to the tumour. We have shown that this mechanism supports multiple animal models of skin, breast, and cervical cancer. Our results demonstrate that fructose is transformed into other nutrients such as LPCs by non-malignant, fructolytic tissues. Fructose-derived LPCs are transferred to the tumours, where they are used to support membrane synthesis. Beyond LPCs, it is likely that other fructose-derived nutrients are also transferred from fructolytic tissues to tumours. Inhibiting fructose metabolism in fructolytic tissues with PF-06835919 reduces circulating LPCs and slows the growth of tumours in animals consuming high levels of fructose. All experiments in this figure were performed once. P values determined by ordinary one-way ANOVA using Dunnett’s test comparing all conditions to the control (a-d, g) and ordinary one-way ANOVA with Tukey’s multiple comparisons test (f). P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, and n.s. is not significant. All data shown as mean ± standard deviation.

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