TERT biology and function in cancer: beyond immortalisation

Abstract

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 ofTERTtranscription/activity is detected in 80–90% of malignant tumours. In several types of cancer, there is a relationship between the presence ofTERTpromoter mutations,TERTmRNA expression and clinicopathological features, but the biological bridge between the occurrence ofTERTpromoter mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence ofTERTpromoter 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 implyTERTtranscription reactivation/activity with cell proliferation, tumour invasion and metastisation. A particular attention is given to the putative connections betweenTERTtranscriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin.