Table 1 Warburg and Reverse Warburg effects

Aerobic glycolysis, or the Warburg effect, is a phenomenon in cancer cells that results in reorientation of metabolism to the glycolytic pathway and to conversion of pyruvate resulting from glycolysis into lactate even in the presence of oxygen. This metabolic reprogramming is a step in the process of tumorigenesis in many cancers. It is one of the best-described metabolic adaptations arising in cancer cells. It is now established, however, that malignant transformation is not based solely on the Warburg effect. Indeed, tumor cells produce a significant fraction of their ATP via oxidative phosphorylation (OXPHOS). Malignant cells adapt their energetic metabolism to the conditions of the microenvironment, in particular to the oxygenation conditions of the tumor, which has the consequence of creating intra-tumor metabolic heterogeneity (for additional information see [1, 9, 10]). The reverse Warburg effect is observed when anabolic epithelial cancer cells induce aerobic glycolysis in neighboring stromal fibroblasts or neighboring catabolic cancer cells. These catabolic cells (epithelial cancer cells or cancer-associated fibroblasts) secrete catabolites such as lactate, pyruvate (energy metabolites resulting from aerobic glycolysis), free fatty acids, and ketone bodies. Anabolic epithelial cancer cells take up these energy-rich metabolites and use them to fuel OXPHOS. This results in a higher proliferative capacity (see Fig. 1 and [1]). An absence of stromal Cav-1 may be a biomarker for the reverse Warburg effect.