Reactive Oxygen Species and Cancer Stem Cells: Molecular Interactions and Their Implications in Cancer

Abstract

Cancer stem cells (CSCs) in a tumor bulk exhibit self-renewal capacity and contribute to tumor aggressiveness that leads to metastasis, cancer therapeutic resistance and relapse. The normal or tumor cells and CSCs are sensitive to the level of reactive oxygen species (ROS) in them. ROS are highly reactive molecules that are generated as byproducts of the endogenous reduction-oxidation (redox) metabolic reactions. In cells maintaining their redox homeostasis, the normal levels of ROS are involved in various cellular functions, including signaling. However, disruption of the redox homeostasis because of incompetent scavenging mechanism elevates the level of ROS, leading to oxidative stress and irreversible damage to the genomic DNA and/or other biomolecules. Subsequently, this results in altered gene expression, genomic instability, mutations, cellular transformation of normal cells to tumor cells or CSCs, survival of CSCs, and tumorigenesis. These aforementioned abnormalities are associated with increased rate of proliferation of tumor cells, hypoxia, angiogenesis, and epithelial to mesenchymal transition (EMT), tumor aggressiveness, and metastasis in several cancers. CSCs and tumor cells with the elevated levels of ROS, hijack various signaling molecules, thus alter multiple signaling cascades or molecular pathways including the stem cell regulatory pathways, which favor the invasiveness of these cells and their tumor microenvironment (TME). Importantly, the elevated levels of ROS can exhibit antitumorigenic activity to suppress tumorigenesis or protumorigenic activity to promote tumorigenesis, metastasis, and cancer treatment resistance and relapse. Moreover, the interactions between the elevated levels of ROS and CSCs create new networks with other signaling cascades, which ultimately leads to poor prognosis, therapeutic resistance and recurrence of cancer. In this chapter, we focus on the molecular interactions between ROS and CSCs and their effects on the tumor aggressiveness and TME. Furthermore, we discuss about the impact of elevated levels of ROS on the cellular transformation of normal or tumor cells to CSCs, cell signaling in CSCs and tumor cells, and their implications in cancer and its therapy.KeywordsCancer stem cells (CSCs)Reactive oxygen species (ROS)Redox-dependent signalingCancer progressionEpithelial to mesenchymal transition (EMT)InvasivenessMesenchymal to epithelial transition (MET)MetastasisTherapeutic resistanceRelapseDrug development