Telomerase: central regulator of all of the hallmarks of cancer.
The hallmarks of cancer described by Hanahan and Weinberg are properties that cancer cells must possess for successful transformation. It is believed that each of these hallmarks is independently driven. Although elongation of telomeres is thought to be the prime function of reactivated telomerase reverse transcriptase, this activity does not account for all its effects, such as increasing cell proliferation, resistance to apoptosis, and invasion. Recent studies suggest that the telomerase subunit telomerase reverse transcriptase (TERT) has novel molecular functions including transcriptional regulation and metabolic reprogramming. We summarize these functions and discuss how they could directly regulate the various hallmarks of cancer. Finally, we suggest that therapeutics targeting noncanonical telomerase functions may work better than those that target its role in telomere extension.
Division of Cancer Genetics and Therapeutics, Laboratory of NFκB Signaling, Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore 138673.
Kee Chung
KC
Low
Vinay
V
Tergaonkar
D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D019207:beta Carotene / Q000378:metabolism
D016328:NF-kappa B; D019207:beta Carotene; D019098:Telomerase
apoptosis; cancer; hTERT; signaling; telomere