Author Response: Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing is associated with therapeutic response to splicing inhibitor
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Le résumé fourni par la source
Dysregulated pre-mRNA splicing and metabolism are two hallmarks of MYC-driven cancers. Pharmacological inhibition of both processes has been extensively investigated as potential therapeutic avenues in preclinical and clinical studies. However, how pre-mRNA splicing and metabolism are orchestrated in response to oncogenic stress and therapies is poorly understood. Here, we demonstrate that Jumonji Domain Containing 6, Arginine Demethylase and Lysine Hydroxylase, JMJD6, acts as a hub connecting splicing and metabolism in MYC-driven neuroblastoma. JMJD6 cooperates with MYC in cellular transformation by physically interacting with RNA binding proteins involved in pre-mRNA splicing and protein homeostasis. Notably, JMJD6 controls the alternative splicing of two isoforms of glutaminase (GLS), namely kidney-type glutaminase (KGA) and glutaminase C (GAC), which are rate-limiting enzymes of glutaminolysis in the central carbon metabolism in neuroblastoma. Further, we show that JMJD6 is correlated with the anti-cancer activity of indisulam, a “molecular glue” that degrades splicing factor RBM39, which complexes with JMJD6. The indisulam-mediated cancer cell killing is at least partly dependent on the glutamine-related metabolic pathway mediated by JMJD6. Our findings reveal a cancer-promoting metabolic program is associated with alternative pre-mRNA splicing through JMJD6, providing a rationale to target JMJD6 as a therapeutic avenue for treating MYC-driven cancers.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Author Response: Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing is associated with therapeutic response to splicing inhibitor
- Date Crossref
- 20/02/2024
- Éditeur
- eLife Sciences Publications, Ltd
- Type
- peer-review
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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St. Jude Children's Research Hospital Department of Cell and Molecular Biology pays non établi dans la noticeÉtablissement de santé
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University of Tennessee Health Science Center Genomics & Informatics pays non établi dans la noticeUniversité ou école supérieure
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Nationwide Children's Hospital pays non établi dans la noticeÉtablissement de santé
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St Jude Children's Research Hospital Department of Surgery pays non établi dans la noticeÉtablissement de santé
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College of Medicine Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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Abigail Wexner Research Institute Center for Childhood Cancer and Blood Disease pays non établi dans la noticeStructure de recherche
Department of Cell and Molecular Biology — St. Jude Children's Research Hospital, Genomics & Informatics — University of Tennessee Health Science Center et Nationwide Children's Hospital, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.