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Publication : Noncanonical functions of telomerase: implications in telomerase-targeted cancer therapies.

First Author  Li Y Year  2014
Journal  Cancer Res Volume  74
Issue  6 Pages  1639-44
PubMed ID  24599132 Mgi Jnum  J:210731
Mgi Id  MGI:5571772 Doi  10.1158/0008-5472.CAN-13-3568
Citation  Li Y, et al. (2014) Noncanonical functions of telomerase: implications in telomerase-targeted cancer therapies. Cancer Res 74(6):1639-44
abstractText  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-kappaB and Wnt/beta-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.
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