The Warburg theory of cancer postulates that an important driver of tumorigenesis is insufficient respiration due to mitochondrial defects, and concomitant enhancement of lactate production due to increased aerobic glycolysis. We analysed 48 melanoma samples by immunohistochemistry and found that 38% of melanomas are characterized by areas of isolated or combined deficiencies of complexes of the oxidative phosphorylation (OXPHOS) system, whereby the incidence of OXPHOS-deficient areas is associated with an increased Breslow index; 62% of melanomas showed high expression of all OXPHOS complexes. Expression of carbonic anhydrase IX was low, indicating that melanomas generally are well-oxygenated. Expression of HIF-1α and MCT4 was high, which might be a consequence of increased lactate dehydrogenase A levels in melanomas. Our data indicate that there are two types of melanomas: one that features a classic Warburg effect, whereas the other one, despite being glycolytic, maintains a high level of OXPHOS complexes.
| BACKGROUNDThe Warburg effect describes the phenomenon whereby cancer cells generate energy predominantly via glycolysis even if sufficient oxygen is present. At first, it seems paradoxical that tumors would use the relatively inefficient glycolytic pathway instead of oxidative phosphorylation (OXPHOS) for energy production. However, there are several explanations for reprogramming the pathway of ATP generation in cancer cells.A major inducer of the glycolytic response is the transcription factor hypoxia-inducible factor-1α (HIF1α), which mediates a pleiotropic reaction by inducing a plethora of gene products, including glucose