A metabolic crosstalk between liposarcoma and muscle sustains tumor growth
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.
Authors
- Maud Heuillet (ORCID: https://orcid.org/0000-0001-7748-6676)
- Madi Y. Cissé (ORCID: https://orcid.org/0000-0001-6760-3381)
- Laëtitia K. Linares (ORCID: https://orcid.org/0000-0003-1661-2119)
- Coralie Sengenès (ORCID: https://orcid.org/0000-0002-4820-6660)
- Sarah Watson (ORCID: https://orcid.org/0000-0003-4534-8783)
- Nelly Firmin (ORCID: https://orcid.org/0000-0001-5839-6261)
- Nadège Gruel (ORCID: https://orcid.org/0000-0001-6915-8082)
- Laurie Gayte
- M. Larroque
- Romain Riscal (ORCID: https://orcid.org/0000-0001-8969-224X)
- Frédéric Chibon (ORCID: https://orcid.org/0000-0002-6548-2181)
- Pascal Pomiès (ORCID: https://orcid.org/0000-0002-5301-6087)
- Gaëlle Pérot (ORCID: https://orcid.org/0000-0002-6951-3934)
- Floriant Bellvert (ORCID: https://orcid.org/0000-0002-3259-8655)
- Chloé Quignot (ORCID: https://orcid.org/0000-0001-8504-232X)
- Benjamin Fourneaux (ORCID: https://orcid.org/0000-0001-5718-200X)
- Sébastien Carrère (ORCID: https://orcid.org/0000-0002-2348-0778)
- Blanche Riquier-Morcant
- Gabrielle Manteaux (ORCID: https://orcid.org/0009-0009-8167-5782)
- Solenn Jacq (ORCID: https://orcid.org/0009-0001-6457-6477)
- Alix Amsel (ORCID: https://orcid.org/0009-0003-8915-5884)
- Jaime Prieto Romero
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- École Nationale Vétérinaire de Toulouse (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Institut National des Sciences Appliquées de Toulouse (FR)
- Université de Montpellier (FR)
- Université Paris Sciences et Lettres (FR)
- Physiologie et Médecine Expérimentale du Coeur et des Muscles (FR)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Toulouse Mathematics Institute (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s41467-024-51827-3
- Citations
- 3
- Primary Topic
- Sarcoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.26
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Université de Montpellier
- Direction Générale de l’offre de Soins
- Servier
- Région Occitanie Pyrénées-Méditerranée