Cancer cells alter their metabolism in order to support their rapid proliferation and expansion across the body. In particular, tumor cells, rather than fueling glucose in the oxidative phosphorylation pathway, generally use glucose for aerobic glycolysis. In this review, we discuss some of the mechanisms thought to be responsible for the acquisition of a glycolytic phenotype in cancer cells and how the switch towards glycolysis represents a selective growth advantage.
Glucose deprivation can activate oncogenes and these can upregulate proteins involved in aerobic glycolysis. In turn, proteins implicated in increased glycolysis can render tumor cells more resistant to apoptosis. Aerobic glycolysis induces acidification of the tumor environment, favoring the development of a more aggressive and invasive phenotype. Altering the pH around tumors might represent a way to hamper tumor development as suggested by a recent work demonstrating that bicarbonate, which increases the pH of tumors, prevented spontaneous metastatization.
The acquisition of a glycolytic phenotype by transformed cells confers a selective growth advantage to these cells. Interfering with aerobic glycolysis, therefore, represents a potentially effective strategy to selectively target cancer cells.
Department of Physiology, Lausanne University, Lausanne, Switzerland
Correspondence to Christian Widmann, Department of Physiology, Rue du Bugnon 7, 1005 Lausanne, Switzerland Tel: +41 21 692 5123; fax: +41 21 692 5505; e-mail: Christian.Widmann@unil.ch