TERT biology and function in cancer: beyond immortalisation

    1. Paula Soares1,2,3,5
    1. 1Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal
    2. 2Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal
    3. 3Medical Faculty, University of Porto, Porto, Portugal
    4. 4Department of Pathology, Centro Hospitalar S. João, Porto, Portugal
    5. 5Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal
    1. Correspondence should be addressed to P Soares; Email: psoares{at}ipatimup.pt


    Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalisation, is one of the hallmarks of cancer that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80–90% of malignant tumours. In several types of cancer, there is a relationship between the presence of TERT promoter mutations, TERT mRNA expression and clinicopathological features, but the biological bridge between the occurrence of TERT promoter mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence of TERT promoter mutations with metastisation/survival in several types of cancer. In follicular cell-derived thyroid cancer, such mutations are associated with worse prognostic features (age of patients, tumour size and tumour stage) as well as with distant metastases, worse response to treatment and poorer survival. In this review, we analyse the data reported in several studies that imply TERT transcription reactivation/activity with cell proliferation, tumour invasion and metastisation. A particular attention is given to the putative connections between TERT transcriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin.

    • Received 15 December 2016
    • Accepted 5 January 2017
    • Made available online as an Accepted Preprint 5 January 2017
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