Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer
| Autor: | Ru Chen, Günther A. Rezniczek, Sheng Pan, Soo J. Shin, Jeffrey A. Smith, Kimberly A. Kelly, Gerhard Wiche, Teresa A. Brentnall |
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| Rok vydání: | 2013 |
| Předmět: |
Scaffold protein
Proteomics endocrine system diseases Cell Immunoblotting macromolecular substances Biology Exosomes Mass Spectrometry Flow cytometry Mice Microscopy Electron Transmission Pancreatic cancer Cell Line Tumor medicine In Situ Nick-End Labeling Animals Humans DNA Primers Analysis of Variance Multidisciplinary medicine.diagnostic_test Plectin Biological Sciences medicine.disease Flow Cytometry Molecular biology Immunohistochemistry digestive system diseases Microvesicles Gene Expression Regulation Neoplastic medicine.anatomical_structure Cancer research Intracellular Carcinoma Pancreatic Ductal |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 110(48) |
| ISSN: | 1091-6490 |
| Popis: | We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, we found that plectin cell surface localization was attributable to its presence in exosomes secreted from PDAC cells, which is dependent on the expression of integrin β4, a protein known to interact with cytosolic plectin. Moreover, plectin expression was necessary for efficient exosome production and was required to sustain enhanced tumor growth in immunodeficient and in immunocompetent mice. It is now clear that this PDAC biomarker plays a role in PDAC, and further understanding of plectin's contribution to PDAC could enable improved therapies. |
| Databáze: | OpenAIRE |
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