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

June 28, 2021

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

Publicated to:Cancers. 13 (13): 3145- - 2021-07-01 13(13), DOI: 10.3390/cancers13133145

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

Affiliations

CSIC UAM, Dept Canc Biol, Inst Invest Biomed Alberto Sols IIBM, Madrid 28049, Spain - Author

CSIC-UAM - Instituto de Investigaciones Biomédicas Alberto Sols (IIBM) - Author

Inst Ramon y Cajal Invest Sanitaria IRYCIS, Chron Dis & Canc, Area 3, Madrid 28049, Spain - Author

Instituto Ramón y Cajal de Investigación Sanitaria - Author

Johannes Gutenberg Univ Mainz, Inst Toxicol, Univ Med Ctr, D-55131 Mainz, Germany - Author

Koc Univ, Dept Surg, Sch Med, TR-34450 Istanbul, Turkey - Author

Koc Univ, Res Ctr Translat Med, TR-34450 Istanbul, Turkey - Author

Koc Universitesi - Author

Mayo Clin, Gene Regulatory Mech & Mol Epigenet Lab, Gastroenterol Res, Rochester, MN 55905 USA - Author

Mayo Clinic - Author

Ulm Univ, Dept Urol, D-89081 Ulm, Germany - Author

Uniklinik RWTH Aachen - Author

Univ Autonoma Madrid UAM, Dept Biochem, Madrid 28049, Spain - Author

Univ Autonoma Madrid UAM, Dept Prevent Med Publ Hlth & Microbiol, Madrid 28049, Spain - Author

Univ Hosp RWTH Aachen, Dept Hematol Oncol Hemostaseol & Stem Cell Transp, D-52062 Aachen, Germany - Author

Univ Med Ctr Gottingen, Dept Surg, D-37075 Gottingen, Germany - Author

Univ Med Ctr Ulm, Dept Internal Med 1, D-89081 Ulm, Germany - Author

Universidad Autónoma de Madrid - Author

Universitat Ulm - Author

Universitatsklinikum Ulm - Author

Universitatsmedizin Gottingen - Author

Universitätsmedizin Mainz - Author

Abstract

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.

Keywords

cancer stem cellspancreatic cancerself-renewalstemnesstelomeraseCancer stem cellsPancreatic cancerSelf-renewalStemnessTelomeraseTelomere length

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 60/245, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.45. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Weighted Average of Normalized Impact by the Scopus agency: 1.34 (source consulted: FECYT Feb 2024)
Field Citation Ratio (FCR) from Dimensions: 5.12 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-25, the following number of citations:

WoS: 16
Scopus: 16
Europe PMC: 14

Impact and social visibility

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; Turkey; United States of America.

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

Affiliations

Abstract

Keywords

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

Impact and social visibility

Leadership analysis of institutional authors