title: hTERT: another brick in the wall of cancer cells.
abstract: In human cancer, expression of telomerase is positively correlated with tumour aggressiveness and metastatic potential. There is accumulating evidence that hTERT (the catalytic subunit of telomerase) favours an immortal phenotype by blocking programmed cell death (apoptosis) independently of its protective function at the telomere ends. This review summarized existing evidence for the anti-apoptotic role of hTERT in the context of tumour-cell resistance against DNA damage and aims to put hTERT in the context of cell-signal-transduction pathways leading either to survival or cell death. We found evidence that telomerase is cross-linked with many different signalling pathways that regulate cell proliferation, DNA damage repair, and also cell death. Thereby, hTERT survival function seems to occur at early stages of DNA damage recognition. We found some discrepancies in the published data though. Based on our findings, we suggest further exploration is needed of the interplay of the DNA damage response signalling network, including MAPK and p53 family activation, on telomerase regulation. This interaction is probably an important factor for fine tuning of the sensitivity of the cell to genotoxic stress. Using anti-neoplastic agents, further dose relationships on timing and extent of DNA damage, cellular repair and death should be established and correlated with hTERT expression/telomerase activation. Closing the data gaps identified here could profoundly improve our understanding of the relevance of telomerase for protecting the cell against anti-cancer agents and would contribute to developing new strategies for cancer therapy.
authors.affiliation: Freiburg University Medical Centre, Department of Environmental Health Sciences, Breisacher Str. 115 b, 79106 Freiburg i.Br., Germany. Electronic address: evelyn.lamy@uniklinik-freiburg.de.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lamy
authors.affiliation: Freiburg University Medical Centre, Department of Environmental Health Sciences, Breisacher Str. 115 b, 79106 Freiburg i.Br., Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Goetz
authors.affiliation: Freiburg University Medical Centre, Department of Paediatrics and Adolescent Medicine, Division of Paediatric Haematology and Oncology, Mathildenstr. 1, 79106 Freiburg, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Erlacher
authors.affiliation: Freiburg University Medical Centre, Department of Environmental Health Sciences, Breisacher Str. 115 b, 79106 Freiburg i.Br., Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Herz
authors.affiliation: Freiburg University Medical Centre, Department of Environmental Health Sciences, Breisacher Str. 115 b, 79106 Freiburg i.Br., Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mersch-Sundermann
mesh_terms: D017209:Apoptosis; D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*
chemical_list: C509186:TERT protein, human; D019098:Telomerase