The metabolic alterations of cancer cells.

ABSTRACT

Cancer cells exhibit profound metabolic alterations, allowing them to fulfill the metabolic needs that come with increased proliferation and additional facets of malignancy. Such a metabolic transformation is orchestrated by the genetic changes that drive tumorigenesis, that is, the activation of oncogenes and/or the loss of oncosuppressor genes, and further shaped by environmental cues, such as oxygen concentration and nutrient availability. Understanding this metabolic rewiring is essential to elucidate the fundamental mechanisms of tumorigenesis as well as to find novel, therapeutically exploitable liabilities of malignant cells. Here, we describe key features of the metabolic transformation of cancer cells, which frequently include the switch to aerobic glycolysis, a profound mitochondrial reprogramming, and the deregulation of lipid metabolism, highlighting the notion that these pathways are not independent but rather cooperate to sustain proliferation. Finally, we hypothesize that only those genetic defects that effectively support anabolism are selected in the course of tumor progression, implying that cancer-associated mutations may undergo a metabolically convergent evolution.