Abstract
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.
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Abbreviations
- hTERT:
-
human telomerase reverse transcriptase
- ATRA:
-
all-trans retinoic acid
- GFP:
-
green fluorescent protein
- TNF:
-
tumor necrosis factor
- TRAIL:
-
TNF-related apoptosis-inducing ligand
- DR:
-
death receptor
- DAPI:
-
diamino-2-phenyl-indol
- APL:
-
acute promyelocytic leukemia
- TUNEL:
-
terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling
- TRAP:
-
telomeric repeat amplification protocol
- TA:
-
telomerase activity
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Acknowledgements
This work was supported by INSERM, the Ligue contre le Cancer, and Association pour la Recherche contre le Cancer (ARC nos. 4513 and 3416). FP and AS were funded by the Fondation pour la Recherche Médicale (FRM).
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Dudognon, C., Pendino, F., Hillion, J. et al. Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance. Oncogene 23, 7469–7474 (2004). https://doi.org/10.1038/sj.onc.1208029
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DOI: https://doi.org/10.1038/sj.onc.1208029
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