A metabolic crosstalk between liposarcoma and muscle sustains tumor growth

Gabrielle Manteaux, Alix Amsel, Blanche Riquier-Morcant, Jaime Prieto Romero, Laurie Gayte, Benjamin Fourneaux, Marion Larroque, Nadège Gruel, Chloé Quignot, Gaelle Perot, Solenn Jacq, Madi Y. Cisse, Pascal Pomiès, Coralie Sengenes, Frédéric Chibon, Maud Heuillet, Floriant Bellvert, Sarah Watson, Sebastien Carrere, Nelly Firmin, Romain Riscal () and Laetitia K. Linares ()
Additional contact information
Gabrielle Manteaux: Université de Montpellier, Institut régional du Cancer de Montpellier
Alix Amsel: Université de Montpellier, Institut régional du Cancer de Montpellier
Blanche Riquier-Morcant: Université de Montpellier, Institut régional du Cancer de Montpellier
Jaime Prieto Romero: Université de Montpellier, Institut régional du Cancer de Montpellier
Laurie Gayte: Université de Montpellier, Institut régional du Cancer de Montpellier
Benjamin Fourneaux: Université de Montpellier, Institut régional du Cancer de Montpellier
Marion Larroque: Université de Montpellier, Institut régional du Cancer de Montpellier
Nadège Gruel: PSL Research University, Institut Curie Research Center
Chloé Quignot: PSL Research University, Institut Curie Research Center
Gaelle Perot: Université Paul Sabatier Toulouse-III
Solenn Jacq: Université de Montpellier, Institut régional du Cancer de Montpellier
Madi Y. Cisse: Université de Montpellier, Institut régional du Cancer de Montpellier
Pascal Pomiès: University of Montpellier-INSERM-CNRS
Coralie Sengenes: Université de Toulouse, INSERM 1301, CNRS 5070, EFS, ENVT
Frédéric Chibon: Université Paul Sabatier Toulouse-III
Maud Heuillet: Université de Toulouse, CNRS, INRA, INSA
Floriant Bellvert: Université de Toulouse, CNRS, INRA, INSA
Sarah Watson: PSL Research University, Institut Curie Research Center
Sebastien Carrere: Université de Montpellier, Institut régional du Cancer de Montpellier
Nelly Firmin: Université de Montpellier, Institut régional du Cancer de Montpellier
Romain Riscal: Université de Montpellier, Institut régional du Cancer de Montpellier
Laetitia K. Linares: Université de Montpellier, Institut régional du Cancer de Montpellier

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51827-3

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