Sirtuins in Cancer – Emerging Role as Modulators of Metabolic Reprogramming

Abstract

Cancer remains one of the leading causes of death worldwide. Among the many alterations found in cancer cells compared to normal cells is a rewiring of cellular metabolism. Many cancer cells exhibit increased glucose consumption, high glycolysis, and elevated lactate secretion. These alterations occur independent of obvious physiologic need, such as hypoxia when oxygen supply is limited and mitochondrial oxidation of glucose becomes restricted. While this increased aerobic glycolysis – now termed the Warburg effect – is the best characterized metabolic reprogramming in cancers, cancer cells also utilize glutamine and fatty acids differently from normal cells. Together, these metabolic changes offer proliferative advantage by fueling biosynthetic pathways. Sirtuin proteins are critical nutrient sensors within the cell that modulate metabolism and have been found to play important roles in rewiring tumor metabolism. In this chapter, we will discuss the role of sirtuins in cancer, especially focusing on how they modulate cancer cell metabolism.