Aberrant accumulation of cyclin D1 rewires glutamine metabolism via loss of IDH3 generating metabolic vulnerability in ESCC and HNSCC

ABSTRACT:

Excessive cyclin D1 accumulation is a frequent oncogenic event in head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC). Although classically associated with enhanced proliferation and genomic instability, we reveal that cyclin D1 dysregulation induces unexpected metabolic dependencies. We define the resulting metabolic rewiring and the underlying mechanism in both established cell models and a newly developed HNSCC mouse model expressing degradation-resistant cyclin D1T286A mutant on a gain-of-function p53R172H background. We demonstrate that sustained nuclear retention of cyclin D1 drives metabolic reprogramming through activation of CDK4/6 and downregulation of mitochondrial isocitrate dehydrogenase 3 (IDH3). This metabolic alteration profoundly sensitizes cells to glutamine deprivation. In this study, we utilized GC-MS to analyze where glutamine is being used and the metabolite changes in cyclin D1 mutant cells.

INSTRUMENT(S): Gas Chromatography MS - positive

PROVIDER: MTBLS13687 | MetaboLights | 2026-08-24

REPOSITORIES: MetaboLights