Tumor cell redox state and mitochondria at the center of the non-canonical activity of telomerase reverse transcriptase.
Telomerase (hTERT) activation in cancer cells is an invariable finding resulting in the maintenance of telomere lengths and enhanced replicative capacity. Therefore a variety of therapeutic approaches are being investigated to target hTERT, such as hTERT-promoter driven expression of apoptosis inducing genes, inhibiting telomeric RNA (hTR), and anti-sense or siRNA mediated gene silencing. Whereas, the conventional oncogenic role of hTERT has been linked to its ability to induce replicative senescence and immortalization, evidence is accumulating to support non-canonical activity of hTERT in cancer cells. To that end, hTERT has been implicated in redox-mediated events and its expression has been shown to impact cellular redox status via the recruitment of the mitochondria, a critical intracellular source of reactive oxygen species (ROS). Further evidence in support of the role of mitochondria in hTERT biology comes from findings demonstrating localization of hTERT to the mitochondria, and the ability of hTERT inhibitors to induce mitochondrial-dependent apoptosis in target cells. Here we review the emerging evidence to support the involvement of the mitochondria and intracellular ROS as critical mediators of the non-canonical functions/activity of hTERT with potential implications for its therapeutic targeting in cancer cells.
Indran
Inthrani Raja
IR
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hande
Manoor Prakash
MP
Pervaiz
Shazib
S
D000818:Animals; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*
D017382:Reactive Oxygen Species; D019098:Telomerase