TERT biology and function in cancer: beyond immortalization.

Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalization, is one of cancer hallmarks 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 to 90% of malignant tumours. In several types of cancer there is a relationship between the presence of TERTp mutations, TERT mRNA expression and clinico-pathological features but the biological bridge between the occurrence of TERTp mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence of TERTp mutations metastization/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 metastization. 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.
PMID: 28057768 DOI: 10.1530/JME-16-0195
[PubMed - as supplied by publisher]