Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells.
cancer stem cells
pancreatic cancer
self-renewal
stemness
telomerase
telomere length
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
23 Jun 2021
23 Jun 2021
Historique:
received:
04
05
2021
revised:
14
06
2021
accepted:
18
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
3
7
2021
Statut:
epublish
Résumé
To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the "stemness" maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.
Identifiants
pubmed: 34201898
pii: cancers13133145
doi: 10.3390/cancers13133145
pmc: PMC8268125
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Deutsche Krebshilfe
ID : 111746
Organisme : Deutsche Krebshilfe
ID : 70112505
Organisme : Deutsche Forschungsgemeinschaft
ID : 316249678 - SFB 1279
Organisme : Medizinische Fakultät, Universität Ulm
ID : L.SBN.0196
Organisme : Hector Foundation
ID : M.65.1
Organisme : Ministerio de Economia y Competitividad
ID : RYC-2012-12104
Organisme : Fundación Asociación Española Contra el Cáncer
ID : GC16173694BARB
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