Tracking down the origin of cancer: metabolic reprogramming as a driver of stemness and tumorigenesis.

Metabolic reprogramming has recently emerged as a fundamental trait of cancer cells. Initially thought to be a consequence of rapid cell proliferation, recent data have reset this idea by demonstrating that metabolic reprogramming can actually drive tumorigenesis. The cancer stem cell (CSC) theory predicts that only a small subpopulation of cancer cells with stem cell properties, which derive from the cancer cell of origin, possesses tumor-initiating potential. However, whether metabolic reprogramming drives tumor formation by regulating the genesis of CSCs is not known. Importantly, the metabolic properties of stem cells and cancer cells are strikingly similar, and metabolic reprogramming is a key factor controlling stemness in these cells. This article reviews the current understanding of cancer metabolism and how it mirrors the metabolic requirements of stem cells. These two concepts are integrated and data demonstrating that metabolic reprogramming regulates CSCs function are discussed, suggesting that metabolic regulation of stemness could be at the origin of cancer.