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Updated: May 12, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the

Arnaldur Hall1, Kathrine Damm Meyle, Marina Krarup Lange

  • 1Genome Integrity Unit, Danish Cancer Society Research Center, Denmark.

Oncotarget
|April 23, 2013
PubMed

Insights

Cancer cells addicted to oncogenes like BRAF rely on glycolysis due to faulty mitochondria. Restoring a key glycolytic enzyme, GAPDH, prevents senescence, revealing metabolism

Area of Science:

  • Molecular Biology
  • Cancer Metabolism
  • Oncology

Background:

  • Oncogene addiction explains cancer cell dependence on specific oncogenes to evade cell death.
  • Targeting oncogenes is a key cancer therapy strategy, but the underlying biochemical mechanisms remain unclear.
  • Understanding the metabolic basis of oncogene addiction is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the metabolic rationale behind addiction to the (V600E)BRAF oncogene in malignant melanoma.
  • To explore the role of glycolysis and oxidative phosphorylation (OXPHOS) in maintaining oncogene addiction.
  • To provide direct evidence linking metabolic pathways to oncogene addiction.

Main Methods:

  • Analysis of glycolysis and oxidative phosphorylation (OXPHOS) in two malignant melanoma cell lines with (V600E)BRAF.
  • Assessment of metabolic changes upon minor reductions in glycolytic activity.
  • Investigation of the effect of (V600E)BRAF inhibition on senescence.
  • Rescue of senescence response by overexpressing glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Main Results:

  • Malignant melanoma cell lines exhibit a strong dependence on glycolysis due to impaired OXPHOS.
  • Reduced glycolysis triggers a reversed Warburg effect, but mitochondria cannot sustain ATP production.
  • (V600E)BRAF maintains glycolytic activity, establishing a metabolic addiction.
  • Overexpression of GAPDH rescues the senescence phenotype induced by (V600E)BRAF inhibition.

Conclusions:

  • Oncogene addiction, specifically to (V600E)BRAF in melanoma, has a significant metabolic foundation.
  • The interplay between glycolysis and OXPHOS is critical for cancer cell survival under oncogene addiction.
  • Metabolic interventions targeting glycolysis could be a viable strategy for treating BRAF-mutant melanomas.

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