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Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target

dc.contributor.authorGarranzo-Asensio, María
dc.contributor.authorSolís-Fernández, Guillermo
dc.contributor.authorMontero-Calle, Ana
dc.contributor.authorGarcía-Martínez, José Manuel
dc.contributor.authorFiuza, María Carmen
dc.contributor.authorPallares, Pilar
dc.contributor.authorGarcía-Jiménez, Custodia
dc.contributor.authorGuzman-Aranguez, Ana
dc.contributor.authorBarderas, Rodrigo
dc.date.accessioned2024-01-30T08:28:09Z
dc.date.available2024-01-30T08:28:09Z
dc.date.issued2022-03-01
dc.identifier.citationMaría Garranzo-Asensio, Guillermo Solís-Fernández, Ana Montero-Calle, José Manuel García-Martínez, Maria Carmen Fiuza, Pilar Pallares, Nuria Palacios-Garcia, Custodia García-Jiménez, Ana Guzman-Aranguez, Rodrigo Barderas; Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target. Diabetes 1 March 2022; 71 (3): 497–510. https://doi.org/10.2337/db20-1206es
dc.identifier.issn0012-1797
dc.identifier.issn1939-327X
dc.identifier.urihttps://hdl.handle.net/10115/29165
dc.description.abstractColorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.es
dc.language.isoenges
dc.publisherAmerican Diabetes Associationes
dc.subjectColorectal cancer and diabeteses
dc.subjectReceptor tyrosine kinase signalinges
dc.subjectPlasma autoantibodieses
dc.subjectReceptor-type tyrosine-protein phosphatase-like N (PTPRN)es
dc.subjectCRC patients survivales
dc.subjectMetastasises
dc.subjectEpithelial-mesenchymal transitiones
dc.titleSeroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Targetes
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doi10.2337/db20-1206es
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses


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