Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells

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....

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Detalles Bibliográficos
Autores: Walter, Karolin, Rodriguez-Aznar, Eva, Ventura Ferreira, Monica S., Frappart, Pierre Olivier, Dittrich, Tabea, Tiwary, Kanishka, Meessen, Sabine, Lerma Martínez, Laura, Daiss, Nora, Schulte, Lucas Alexander, Najafova, Zeynab, Arnold, Frank, Usachov, Valentyn, Azoitei, Ninel, Erkan, Mert, Lechel, Andre, Brümmendorf, Tim H., Seufferlein, Thomas, Kleger, Alexander, Tabares López, Enrique, Günes, Cagatay, Johnsen, Steven A., Beier, Fabian, Sainz, Bruno, Hermann, Patrick C.
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/699619
Acceso en línea:http://hdl.handle.net/10486/699619
https://dx.doi.org/10.3390/cancers13133145
Access Level:acceso abierto
Palabra clave:Cancer stem cells
Pancreatic cancer
Self-renewal
Stemness
Telomerase
Telomere length
Medicina
Descripción
Sumario: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

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