1. A metabolic crosstalk between liposarcoma and muscle sustains tumor growth.
- Author
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Manteaux, Gabrielle, Amsel, Alix, Riquier-Morcant, Blanche, Prieto Romero, Jaime, Gayte, Laurie, Fourneaux, Benjamin, Larroque, Marion, Gruel, Nadège, Quignot, Chloé, Perot, Gaelle, Jacq, Solenn, Cisse, Madi Y., Pomiès, Pascal, Sengenes, Coralie, Chibon, Frédéric, Heuillet, Maud, Bellvert, Floriant, Watson, Sarah, Carrere, Sebastien, and Firmin, Nelly
- Subjects
MUSCLE tumors ,TUMOR growth ,LIPOSARCOMA ,MUSCLE cells ,CELL survival - Abstract
Dedifferentiated and Well-differentiated liposarcoma are characterized by a systematic amplification of the Murine Double Minute 2 (MDM2) oncogene. We demonstrate that p53-independent metabolic functions of chromatin-bound MDM2 are exacerbated in liposarcoma and mediate an addiction to serine metabolism to sustain tumor growth. However, the origin of exogenous serine remains unclear. Here, we show that elevated serine levels in mice harboring liposarcoma-patient derived xenograft, released by distant muscle is essential for liposarcoma cell survival. Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients. During tumorigenesis, liposarcoma has been reported to develop a dependence on serine metabolism but it is unclear how this high energetic demand is met. Here, the authors identify a crosstalk mechanism between tumor and distant muscle cells wherein liposarcoma cell-derived IL-6 drives muscle cell release of serine, in turn accelerating tumor growth. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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