The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer

Journal of Bioenergetics and Biomembranes, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Otto Warburg originally proposed that cancer arose from a two-step process. The first step involved chronic insufficiency of mitochondrial oxidative phosphorylation (OxPhos), while the second protracted compensatory energy synthesis through lactic acid fermentation. His extensive findings showed oxygen consumption was lower lactate production higher in cancerous tissues than non-cancerous tissues. considered both and extracellular as accurate markers for ATP OxPhos glycolysis, respectively. Warburg’s hypothesis challenged showing remained high some cells despite elevated suggesting largely unimpaired. New information indicates neither nor are surrogates quantification cells. also did not know significant amount could come glutamine-driven substrate level glutaminolysis pathway with succinate produced end product, thus confounding linkage to origin within mitochondria. Moreover, new shows cytoplasmic lipid droplets aerobic fermentation biomarkers insufficiency. original can now be linked more complete understanding how underlies dysregulated cell growth. These address several questionable assumptions regarding allowing field advance effective therapeutic strategies less toxic metabolic management prevention cancer.

Language: Английский

ENC1 Promotes the Malignant Progression and Metastasis by Suppressing TRIM21 Mediated Vimentin Degradation in Wilms Tumor

Molecular Carcinogenesis, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Ectodermal neural cortex 1 (ENC1) is significantly upregulated in various cancers and shows a positive correlation with poor prognosis advanced clinical stages, such as colorectal cancer, endometrial cancer breast cancer. However, the role of ENC1 Wilms tumor (WT) has not been previously reported. In this study, we conducted several vitro functional experiments established xenograft models to confirm oncogenic potential ENC1. The binding proteins were identified through co-immunoprecipitation mass spectrometry screen mechanism malignant progression. Further analysis elucidated by which promotes tumorigenesis. results demonstrated that was overexpressed recurrence samples, elevated expression showing significant negative both overall survival recurrence-free patients. Functionally, oncogenicity assessment cell proliferation, migration, invasion capabilities. Mechanistically, immunoprecipitation spectrometry, Vimentin an interacting protein competed E3 ubiquitin ligase TRIM21 for binding, thereby reducing ubiquitination level enhancing its stability. conclusion, study demonstrates functions novel target disrupting TRIM21-mediated Vimentin, presents insights treatment development prognostic markers.

Language: Английский