Noncanonical Functions of Telomerase: Implications in Telomerase-Targeted Cancer Therapies

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 6; pp. 1639 - 1644
• Main Authors: YINGHUI LI, TERGAONKAR, Vinay
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-03-2014
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinogenesis - genetics; Carcinogenesis - metabolism; Enzyme Activation; Feedback, Physiological; Humans; Medical sciences; Molecular Targeted Therapy; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Neoplasms - enzymology; Pharmacology. Drug treatments; Signal Transduction; Telomerase - antagonists & inhibitors; Telomerase - physiology; Telomere Homeostasis; Tumors; Treatment; Malignant tumor; Enzyme; Targeted therapy; Telomerase; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-13-3568

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.