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

Karolin Walter, Eva Rodriguez-Aznar, Monica S. Ventura Ferreira, Pierre Olivier Frappart, Tabea Dittrich, Kanishka Tiwary, Sabine Meessen, Laura Lerma, Nora Daiss, Lucas Alexander Schulte, Zeynab Najafova, Frank Arnold, Valentyn Usachov, Ninel Azoitei, Mert Erkan, Andre Lechel, Tim H. Brümmendorf, Thomas Seufferlein, Alexander Kleger, Enrique TabarésCagatay Günes, Steven A. Johnsen, Fabian Beier, Bruno Sainz, Patrick C. Hermann

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number3145
Issue number13
StatePublished - Jul 1 2021


  • Cancer stem cells
  • Pancreatic cancer
  • Self-renewal
  • Stemness
  • Telomerase
  • Telomere length

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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