A metabolic crosstalk between liposarcoma and muscle sustains tumor growth.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 Sep 2024
12 Sep 2024
Historique:
received:
17
02
2023
accepted:
20
08
2024
medline:
13
9
2024
pubmed:
13
9
2024
entrez:
12
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39266552
doi: 10.1038/s41467-024-51827-3
pii: 10.1038/s41467-024-51827-3
doi:
Substances chimiques
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Serine
452VLY9402
MDM2 protein, human
EC 2.3.2.27
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7940Informations de copyright
© 2024. The Author(s).
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