title: 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 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.
authors.affiliation: Institute of Molecular Pathology and ImmunologyUniversity of Porto (IPATIMUP), Porto, Portugal.|Institute for Research and Innovation in Health (I3S)University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Pestana
authors.affiliation: Institute of Molecular Pathology and ImmunologyUniversity of Porto (IPATIMUP), Porto, Portugal.|Institute for Research and Innovation in Health (I3S)University of Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.affiliation: Institute of Molecular Pathology and ImmunologyUniversity of Porto (IPATIMUP), Porto, Portugal.|Institute for Research and Innovation in Health (I3S)University of Porto, Porto, Portugal.|Medical FacultyUniversity of Porto, Porto, Portugal.|Department of PathologyCentro Hospitalar S. João, Porto, Portugal.|Department of PathologyMedical Faculty, University of Porto, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Institute of Molecular Pathology and ImmunologyUniversity of Porto (IPATIMUP), Porto, Portugal psoares@ipatimup.pt.|Institute for Research and Innovation in Health (I3S)University of Porto, Porto, Portugal.|Medical FacultyUniversity of Porto, Porto, Portugal.|Department of PathologyMedical Faculty, University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D019098:Telomerase
keywords: TERT; cancer; telomerase; thyroid