Fig. 1: Liposarcoma reprogram serine synthesis pathway in muscles.

A Normalized RNASeq reads of MDM2. (n = 5 normal fat tissues, 5 lipoma and 38 liposarcoma tumors). B Serine and C Glycine levels (μM) measured by HPLC, in nude mice before and 28 days post-engraftment of liposarcoma cells (IB115). Mice were treated daily with placebo or SP141 (40 mg/ml). (n = 3 experimental replicates). D Serine levels (μM) measured by HPLC. Control mice were compared to liposarcoma PDX Mice (LPS-PDX). Mice were treated daily with placebo or SP141 (40 mg/ml). (n = 5 animals/group). E Stable isotope tracing experiments in IB115 cells treated cultured for 48 h in the presence of uniformly labeled [U-13C]Glu and [U-13C]Ser in -Ser/Gly medium. LC-MS was used to detect the relative amount of the 13C-labeled m + 3 isotopolog of intracellular serine. (n = 3 experimental replicates). F Real-time qPCR analysis performed on LPS-PDX and control mice muscle, evaluating expression of serine synthesis pathway genes: Phgdh, Psat1 and Psph. Mice were treated daily with placebo or SP141 (40 mg/ml). (n= 6 animals/group). G Real-time qPCR analysis performed on LPS-PDX and control mice liver, evaluating expression of serine synthesis pathway genes: Phgdh, Psat1 and Psph. Mice were treated daily with placebo or SP141 (40 mg/ml). (n = 5 animals/group). H Real-time qPCR analysis performed control mice liver, evaluating expression of serine synthesis pathway genes: Phgdh, Psat1 and Psph. Mice were fed with normal or -Ser/Gly diet. (n = 3 experimental replicates). I Real-time qPCR analysis performed on control mice muscle, evaluating expression of serine synthesis pathway genes: Phgdh, Psat1 and Psph. Mice were fed with normal or -Ser/Gly diet. (n = 3 experimental replicates). J Real-time qPCR analysis performed on LPS-, Leiomyosarcoma- and Breast cancer-PDXs compared to control mice muscle, evaluating expression of serine synthesis pathway genes: Phgdh, Psat1 and Psph. (n = 5 animals/group). Data are shown as means ± SEM and three or more independent experiments were performed. Statistical tests were all adjusted for multiple comparisons and included two-tailed unpaired t-test for (e, h, i), one-way analysis of variance (ANOVA) for a, b, c, d, f, g and j. *P < 0.05, **P < 0.01, ***<0.001, n.s = non-significant. Source data are provided as a Source Data file.