Author:
Gabrielle Manteaux,Jaime Prieto Romero,Laurie Gayte,Blanche Riquier-Morcant,Alix Amsel,Solenn Jacq,Madi Y Cisse,Gaelle Perrot,Frédéric Chibon,Pascal Pomies,Sebastien Carrere,Nelly Firmin,Romain Riscal,Laetitia K Linares
Abstract
AbstractDedifferentiated (DD-LPS) and Well-differentiated (WD-LPS) liposarcoma are characterized by a systematic amplification of theMDM2oncogene. We recently demonstrated that p53-independent metabolic functions of chromatin-bound MDM2 (C-MDM2) are exacerbated in LPS and mediate an addiction to serine metabolism in order to sustain tumor growth. Here, we show that metabolic cooperation between LPS and distant muscle, which raise serine and glycine blood levels, is essential for LPS tumor growth. By releasing IL-6, tumor influence distant muscle to upregulate their serine synthesis machinery. Blocking IL-6 secretion or treating LPS cells with FDA approved IL-6 inhibitor, decreased serine production and impaired tumor proliferation. These data reveal IL-6 as a central tumorkine in metabolic crosstalk between tissues and identifies IL-6 as a plausible treatment for LPS patients.
Publisher
Cold Spring Harbor Laboratory
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