title: Noncanonical functions of telomerase: implications in telomerase-targeted cancer therapies.
abstract: Telomerase plays a pivotal role in bypassing cellular senescence and maintaining telomere homeostasis, essential properties required for the sustenance and progression of cancer. However, recent investigations have uncovered extratelomeric properties of telomerase that are independent of its role in telomere extension. This review summarizes recent insights to the noncanonical functions of telomerase reverse transcriptase (TERT) catalytic subunit, in particular in cancer progression, and highlights two major signaling mechanisms involved in the cross-talk with TERT-the NF-κB and Wnt/β-catenin pathways. We propose a feed-forward regulatory loop mechanism underlying TERT activation in cancers in which TERT acts as a transcriptional modulator of oncogenic signaling pathways that sustain its own levels and control the induction of target genes critical for tumor cell survival and proliferation. Finally, we provide a new perspective on telomerase-targeted cancer therapies and suggest possible interventions targeting the nontelomeric roles of TERT. This therapeutic strategy can be used in the future targeting of other telomerase components that exhibit novel nontelomeric functions in cancer and other ailments.
authors.affiliation: Authors' Affiliations: Division of Cancer Genetics and Therapeutics, Laboratory of NF-κB Signaling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR); and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Vinay
authors.initials: V
authors.lastname: Tergaonkar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D025461:Feedback, Physiological; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D015398:Signal Transduction; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000502:physiology*; D059505:Telomere Homeostasis
chemical_list: D000970:Antineoplastic Agents; D019098:Telomerase