Reactive Oxygen Species in Stem Cell Proliferation and Cancer

Abstract

Reactive oxygen species (ROS) are chemically reactive species derived from oxygen molecule and can easily react with a variety of other molecules present in the cells. ROS are produced during cellular respiration in mitochondria and other organelles such as peroxisome, endoplasmic reticulum (ER), and phagocytes, where they play a prominent role in a variety of cellular activities such as proliferation, cancer development, differentiation, etc. ROS are also produced by fatty acid oxidation and oxidative burst of immune cells. Among all the known pathways of ROS production, mitochondrial oxidative phosphorylation contributes the most to their production. It has been found that the inner mitochondrial membrane contributes about 80% of free radicals, and the remaining 20% are generated in the matrix. ROS regulate signaling pathways through various transcription factors which either up- or down-regulate the cascade of signaling thus lead to proliferation, differentiation and maintenance of stem cell pluripotency and cancer development. Most of the time, ROS regulate proliferation by controlling cell cycle with pRB and E2F genes. The ROS phosphorylate these transcription factors with the help of cyclin-dependent kinases (CDKs). Stem cells are cells with the unique ability to self-renew and differentiate into specialized cell type in the availability of suitable transcription factors. Proliferation of these cells is achieved through tight regulation of genes such as OCT4, SOX2, KLF4, etc. It has been proved that the normal level of ROS is crucial for stem cell proliferation and differentiation, but any change in ROS level may result in cancer progression by inactivation of tumor suppression gene and activation of oncogenes. This chapter focuses on ROS-mediated signaling, stem cells speciation, and cancer development through stem cells.