Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance.
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.
INSERM U496, Institut d'Hématologie, Hôpital Saint-Louis, 1, Avenue Claude Vellefaux, 75010 Paris, France.
Charles
C
Dudognon
Frédéric
F
Pendino
Josette
J
Hillion
Anne
A
Saumet
Michel
M
Lanotte
Evelyne
E
Ségal-Bendirdjian
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D019098:Telomerase / Q000378:metabolism* / Q000502:physiology*; D016615:Telomere; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; D014212:Tretinoin; D019098:Telomerase