Implications of ROS in Cancer Stem Cells Mechanism of Action

Abstract

Cancer stem cells (CSCs) are self-renewal cells involved in tumor progression and recurrence. Cell transformation and reprogramming in CSCs are the results of complex processes, including metabolic changes from glycolytic to oxidative phosphorylation or vice versa. CSCs have a large spectrum, displaying a quiescent status and an embryonic signature. Their activity is influenced by the tumor microenvironment and they are using different signaling pathways for maintenance. Reactive oxygen species (ROS) induce mutations, being involved in the modulation of signal transduction pathways or gene transcription factors which lead to alterations of oncogene expression and tumor progression. CSCs gain an increased resistance in case of increased ROS level, manifested by a reduced oxidative injury and a longer survival. Epigenetic changes induced by chronic inflammation, excessive redox stress, and hypoxic environment stimulate the plasticity of the transition between CSCs and non-CSCs. Oxidative stress may influence tumor development and progression, as recent evidences show a persistent prooxidant state in tumor cells. As a consequence, multiple sequences of tumor progression, such as alteration of cell adhesion, stimulation of tumor angiogenesis, increased matrix metalloproteinases (MMPs) activity, and epithelial-mesenchymal transition (EMT), are associated with the oxidative stress and ROS. The exploitation of ROS dual abilities in the occurrence, development, and evolution of CSCs may be useful for the development of new therapeutic strategies targeting redox regulatory mechanisms. The adaptive resistance of CSCs emphasizes the importance of simultaneous blockage of multiple signaling pathways as a possible therapeutic approach which may overcome CSCs resistance, opening encouraging perspectives.