Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance

• Published in: Oncogene Vol. 23; no. 45; pp. 7469 - 7474
• Main Authors: DUDOGNON, Charles, PENDINO, Frédéric, HILLION, Josette, SAUMET, Anne, LANOTTE, Michel, SEGAL-BENDIRDJIAN, Evelyne
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 30.09.2004; Nature Publishing Group
• Subjects: Acute promyeloid leukemia; Ageing, cell death; Apoptosis; Apoptosis - physiology; Apoptosis Regulatory Proteins; Biological and medical sciences; Cancer; Cell death; Cell growth; Cell immortalization; Cell physiology; Cell receptors; Cell structures and functions; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cisplatin; DNA-Binding Proteins; Drugs; Etoposide; Fundamental and applied biological sciences. Psychology; Green Fluorescent Proteins; Health aspects; Humans; Immortalization; Leukemia; Ligands; Luminescent Proteins - metabolism; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - physiology; Miscellaneous; Molecular and cellular biology; Physiological aspects; Promyeloid leukemia; Proteins; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor - physiology; Retinoic acid; Retinoids; Signal Transduction; Structure; Telomerase; Telomerase - metabolism; Telomerase - physiology; Telomerase reverse transcriptase; Telomere; Telomeres; TNF-Related Apoptosis-Inducing Ligand; TRAIL protein; Tretinoin - pharmacology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - physiology; Tumor necrosis factor-TNF; Tumorigenesis; Tumors; France; TRAIL; Enzyme; Chromosome; Death; ATRA; Carcinogenesis; Telomerase; Telomere; APL; Apoptosis; Biological receptor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208029

Human telomerase has been implicated in cell immortalization and cancer. Recent works suggest that telomerase confers additional function required for tumorigenesis that does not depend on its ability to maintain telomeres. This new action may influence tumor therapy outcomes by yet unraveled mechanisms. Here, we show that overexpression of the catalytic subunit of telomerase (hTERT) protects a maturation-resistant acute promyelocytic leukemia (APL) cell line from apoptosis induced by the tumor necrosis factor (TNF) or TNF-related apoptosis-inducing ligand (TRAIL) and not from apoptosis induced by chemotherapeutic drugs such as etoposide or cisplatin. Conversely, in these cells, TRAIL-induced cell death is magnified by all-trans retinoic acid (ATRA) treatment, independently of telomerase activity on telomeres. Of note, this response is subordinated neither to maturation nor to telomere shortening. This work underlines that retinoids and death receptor signaling cross-talks offer new perspectives for antitumor therapy.