dc.contributor
Institut Català de la Salut
dc.contributor
[Arbel Rubinstein T, Reuveni I, Hesin A] Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. [Klein-Goldberg A] Institute of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel. [Olauson H] Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14186 Stockholm, Sweden. [Larsson TE] Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14186 Stockholm, Sweden. Department of Nephrology, Karolinska University Hospital, 17176 Stockholm, Sweden. [Bosch A] Klogenix Therapeutics Inc., Boston, MA 02116, USA. Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERNED, Instituto de Salud Carlos III, 28029 Madrid, Spain. [Chillón M] Klogenix Therapeutics Inc., Boston, MA 02116, USA. Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. ICREA, Institut Catalan Recerca Avançada, 08010 Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Arbel Rubinstein, Tammi
dc.contributor.author
Reuveni, Inbal
dc.contributor.author
Hesin, Arkadi
dc.contributor.author
Klein-Goldberg, Anat
dc.contributor.author
Olauson, Hannes
dc.contributor.author
Larsson, Tobias E.
dc.contributor.author
Bosch Merino, Assumpció
dc.contributor.author
Chillon Rodriguez, Miguel
dc.date.accessioned
2025-10-24T08:54:54Z
dc.date.available
2025-10-24T08:54:54Z
dc.date.issued
2022-03-14T13:41:50Z
dc.date.issued
2022-03-14T13:41:50Z
dc.identifier
Arbel Rubinstein T, Reuveni I, Hesin A, Klein-Goldberg A, Olauson H, Larsson TE, et al. A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy. Cancers (Basel). 2021 Dec;13(24):6297.
dc.identifier
https://hdl.handle.net/11351/7174
dc.identifier
10.3390/cancers13246297
dc.identifier
000747670700001
dc.identifier.uri
http://hdl.handle.net/11351/7174
dc.description.abstract
Klotho; Càncer de pàncrees; Supressor del tumor
dc.description.abstract
Klotho; Cáncer de páncreas; Supresor de tumor
dc.description.abstract
Klotho; Pancreatic cancer; Tumor suppressor
dc.description.abstract
Klotho is an anti-aging transmembrane protein, which can be shed and can function as a hormone. Accumulating data indicate that klotho is a tumor suppressor in a wide array of malignancies, and designate the subdomain KL1 as the active region of the protein towards this activity. We aimed to study the role of klotho as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Bioinformatics analyses of The Cancer Genome Atlas (TCGA) datasets revealed a correlation between the survival of PDAC patients, levels of klotho expression, and DNA methylation, and demonstrated a unique hypermethylation pattern of klotho in pancreatic tumors. The in vivo effects of klotho and KL1 were examined using three mouse models. Employing a novel genetic model, combining pancreatic klotho knockdown with a mutation in Kras, the lack of klotho contributed to PDAC generation and decreased mousece survival. In a xenograft model, administration of viral particles carrying sKL, a spliced klotho isoform containing the KL1 domain, inhibited pancreatic tumors. Lastly, treatment with soluble sKL prolonged survival of Pdx1-Cre; KrasG12D/+;Trp53R172H/+ (KPC) mice, a model known to recapitulate human PDAC. In conclusion, this study provides evidence that klotho is a tumor suppressor in PDAC. Furthermore, these data suggest that the levels of klotho expression and DNA methylation could have prognostic value in PDAC patients, and that administration of exogenous sKL may serve as a novel therapeutic strategy to treat PDAC.
dc.description.abstract
This project was funded by the The Sami and Tova Sagol Foundation for the Study of Aging, the Margaret Stultz foundation for Pancreatic Cancer Research, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Ministerio de Ciencia e Innovación ‘Proyectos I+D+I 2019, to M.C., (grant number PID2019-104034RB-I00) and by the TASMC excellence fund. to I.W.
dc.format
application/pdf
dc.format
application/pdf
dc.relation
Cancers;13(24)
dc.relation
https://doi.org/10.3390/cancers13246297
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Pàncrees - Càncer - Tractament
dc.subject
Proteïnes supressores de tumors
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de neoplasias::proteínas supresoras de tumor
dc.title
A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
