ROS and oncogenesis with special reference to EMT and stemness
Graphical abstract
Section snippets
Reactive oxygen species (ROS) and its varieties
Reactive oxygen species (ROS) are the radicals having single unpaired electron in the outermost electron shell which makes them highly reactive in nature. ROS can exist in two forms- either as free oxygen viz. superoxide, nitric oxide, hydroxyl radical, sulphoxyl radicals etc. or as non-radical species viz. oxygen singlet, ozone, hydrogen peroxide, highly reactive derivatives of lipid or carbohydrate etc. (Liou and Storz, 2010). Superoxide, hydrogen peroxide, nitric oxide and hydroxyl radicals
Cellular origin of ROS and its biological fate
Primary source of intracellular superoxide constitutes of the NADPH oxidase (NOXs) mediated oxidation of NADPH (Bedard and Krause, 2007). Mitochondrial electron leakage during aerobic respiration can also account for the superoxide generation (Jastroch et al., 2010). Within the cell superoxide gets converted into hydrogen peroxide in presence of superoxide dismutase. Generated hydrogen peroxide can oxidize the cystein residues of certain proteins to initiate redox signaling cascade. In other
Redox signaling and redox modulation
Transduction of cellular signaling involves the binding of extracellular stimulus (“first messenger”) with the receptor protein of the cell and the activated receptor can in turn activate other signaling molecules (“second messengers”). Finally, the signal is distributed to the appropriate targets through the activation of one or more signaling molecules resulting in the altered behavior of the cell. Low level of ROS produced by the process such as mitochondrial respiration or by the action of
Physiological and pathophysiological consequences of ROS
ROS has vital physiological attribution in biological system. Phagocytic cells depend on the production of intracellular ROS for the destruction of engulfed pathogen, an important aspect of innate immunity (Paiva and Bozza, 2014). As mentioned in the previous section, ROS can induce physiological response by acting as second messenger during redox signaling. Anti-oxidant can interfere with the physiological role of ROS to cause undesired consequences. It has been reported that the
CSCs
CSC hypothesis throw light on a quiescent sub-population of the bulk tumor cells that can withstand chemo and radiation therapies and accounts for the recurrence of the tumor (Zheng et al., 2013Kim et al., 2009aPhi et al., 2018) [Fig. 3]. Many studies identified CSCs as the main cause of cancer relapse (Peitzsch et al., 2017Ayob and Ramasamy, 2018Li et al., 2018). These cells possesses the stem cell properties viz. self-renewal, differentiation and are also tumorogenic when transplanted into an
Future directions
ROS has emerged as a critical factor in oncogenesis. Depending on the signaling cascade triggered, ROS can act as either tumor suppressor or tumor promoter. Moreover, ROS has the potency to promote EMT especially in hypoxic environment which may lead to the development of quiescent, drug/ chemo resistant CSC population that acts as the “cancer seed”. Thereafter the sharp paradoxical phenomenon of decline of ROS level happens in CSC to maintain the stemness property. The detailed mechanism for
Declaration of Competing Interest
Authors declare no potential conflict of interest.
Acknowledgements
Financial support from the DBT-RA Program in Biotechnology and Life Sciences is gratefully acknowledged. The work was supported by the grant from the Department of Science and Technology, Government of West Bengal, India (151(sanc.)/ST/P/S&T/ 9G-32/2016; Dated. 8.2.2018).
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