RT Journal Article T1 Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target A1 Garranzo Asensio, María A1 Solís Fernández, Guillermo A1 Montero Calle, Ana A1 García Martínez, José Manuel A1 Fiuza, María Carmen A1 Pallares, Pilar A1 Palacios García, Nuria A1 García Jiménez, Custodia A1 Guzmán Aránguez, Ana Isabel A1 Barderas Manchado, Rodrigo AB Colorectal 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. We explore here the value of autoantibodies against receptor-type tyrosineprotein phosphatase-like N PTPRN (full-length or selected domains) as diagnostic markers using a cohort of type 2 diabetic (T2D), CRC, healthy individuals or patients with both diseases. We show that PTPRN autoantibody levels in plasma discriminated between T2D patients with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of CRC patients. 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 T2D patients at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidences that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in CRC patients. PB American Diabetes Association SN 0012-1797 YR 2022 FD 2022-03 LK https://hdl.handle.net/20.500.14352/72468 UL https://hdl.handle.net/20.500.14352/72468 LA eng NO Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. NO Ministerio de Economía y Competitividad (MINECO)/FEDER NO Instituto de Salud Carlos III (ISCIII)/FEDER NO Ministerio de Educación DS Docta Complutense RD 14 dic 2025