1. Figure 2 Metabolic heterogeneity in tumours
Figure 2 | Metabolic heterogeneity in tumours. Within tumours, cancer-cell metabolism can vary depending on influences of the tumour microenvironment and the distance to the vasculature. Cancer cells located closer to the blood supply profit from their access to nutrients and oxygen, and generate ATP aerobically via oxidative phosphorylation and upregulate anabolic pathways, supporting rapid proliferation. The oxidative stress caused by these rapidly proliferating cancer cells induces glycolysis and autophagy in the surrounding stromal cells that generates catabolites, such as lactate or ketones, which in turn are taken up by anabolic cancer cells, and used to fuel mitochondrial metabolism and ATP production (reverse Warburg effect). Similarly, low nutrient availability requires that tumour cells located further from the vasculature and in proximity to anabolic tumour-cell populations commit to alternative catabolic metabolic pathways, such as autophagy, allowing greater adaptability to meet their resources and energy needs. ATP, adenosine triphosphate; HIF-1α, hypoxia-inducible factor 1α; JNK/AP1, c-Jun N-terminal kinases/activator protein 1; MCT1, monocarboxylate transporter 1; MCT4, monocarboxylate transporter 4; NFκB, nuclear factor κB; TGF-β, transforming growth factor β.
Martinez-Outschoorn, U. E. et al. (2016) Cancer metabolism: a therapeutic perspective
Nat. Rev. Clin. Oncol. doi: /nrclinonc