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. 2021 Apr 27;10:e59809. doi: 10.7554/eLife.59809

Figure 7. Methionine regulates Src-induced Tor signaling, tissue growth, and organismal lethality.

(A) Addition of essential amino acids enhances organismal lethality caused by Src42A constitutively active (CA) expression in the wing disc, whereas addition of non-essential amino acids does not. Kruskal-Wallis test with Dunn’s post-test. (B) Only methionine subtraction from the diet improves organismal survival over the Src42A CA stress. One-way ANOVA with Sidak’s post-test. (C) Addition of methionine reduces organismal survival over the Src42A CA stress in a dose-dependent manner. One-way ANOVA with Sidak’s post-test. (D) An amount of methionine in the hemolymph was measured by LC-MS/MS. Expression of Src42A CA in the wing disc decreases the circulating methionine in the hemolymph. Two-tailed unpaired t-test. (E-F) Dietary methionine activates both cell proliferation and phosphorylation of 4EBP that are induced by Src42A CA and JNK DN. (G) Quantification of the total volume of GFP+ cells (µm³) in E-F. Mann-Whitney test. (H) Quantification of phosphorylated 4EBP in E-F. Two-tailed unpaired t-test. (I) SamS knockdown suppresses phosphorylation of 4EBP and overgrowth induced by Src42A CA and JNK DN. (J) Quantification of the total volume of GFP+ cells (µm³) in I. One-way ANOVA with Sidak’s post-test. (K) Quantification of phosphorylated 4EBP in I. One-way ANOVA with Sidak’s post-test. Scale bars, 100 µm.

Figure 7.

Figure 7—figure supplement 1. Involvement of amino acids in Src-induced oncogenic stress.

Figure 7—figure supplement 1.

(A) Methionine addition does not affect survival of control flies without tumor burden. One-way ANOVA with Sidak’s post-test. (B) The graph shows which stage animals could reach. Dietary restriction of yeast suppresses organismal lethality induced by Src42A constitutively active (CA) overexpression with JNK inhibition. Methionine supplementation suppresses the dietary restriction-mediated effect on organismal lethality. (C) The concentrations of EAAs in the hemolymph were measured by CE-MS. (D) The concentrations of NEAAs in the hemolymph were measured by CE-MS.

Figure 7—figure supplement 2. Involvement of methionine in Src-induced Tor activation.

Figure 7—figure supplement 2.

(A) Neither dietary restriction of yeast nor methionine supplementation affects Src42A constitutively active (CA)-induced apoptosis. (B-C) Dietary restriction of yeast reduces the wing tissue development, which is estimated by the size of wings. Methionine supplementation does not rescue the tissue growth defects caused by yeast restriction. One-way ANOVA with Sidak’s post-test. (D) Samtor knockdown enhances Tor activation induced by Src42A CA and JNK DN in a diluted yeast condition, where Tor activation is suppressed. On the other hand, the overgrowth phenotype induced by Src42A CA and JNK DN was suppressed. (E) Quantification of the total volume of GFP+ cells (µm³) in D. Two-tailed unpaired t-test. (F) Quantification of phosphorylated S6 in D. Two-tailed unpaired t-test. Scale bars, 100 µm.