Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer
Autor: | Eric J. Huang, David H. Rowitch, John C. Silbereis, Lawrence R. Shiow, Tracy J. Yuen, Stavros Lomvardas, Stephen P.J. Fancy, Sergio E. Baranzini, Emily P. Harrington |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Colorectal cancer
Cellular differentiation Diseases medicine.disease_cause Transgenic Mice Random Allocation Leukoencephalopathies 2.1 Biological and endogenous factors Psychology Aetiology Hypoxia Wnt Signaling Pathway Cancer Pediatric Mutation biology General Neuroscience Wnt signaling pathway LRP6 LRP5 Cell Differentiation Up-Regulation Colo-Rectal Cancer Oligodendroglia medicine.anatomical_structure Neurological Colonic Neoplasms Stem Cell Research - Nonembryonic - Non-Human Female Cognitive Sciences Adenomatous polyposis coli 1.1 Normal biological development and functioning Adenomatous Polyposis Coli Protein Article Underpinning research medicine Genetics Animals Humans Genetic Association Studies Neurology & Neurosurgery Neurosciences Infant Perinatal Period - Conditions Originating in Perinatal Period medicine.disease Stem Cell Research Newborn Oligodendrocyte Brain Disorders Wnt Proteins Gene Expression Regulation Brain Injuries Immunology Cancer research biology.protein Digestive Diseases Neuroscience Biomarkers |
Zdroj: | Nature neuroscience Nature neuroscience, vol 17, iss 4 |
ISSN: | 1546-1726 1097-6256 |
Popis: | In colon cancer, mutation of the Wnt repressor APC (encoding adenomatous polyposis coli) leads to a state of aberrant and unrestricted high-activity signaling. However, the relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct functional states of Wnt activity determine oligodendrocyte precursor cell (OPC) differentiation and myelination. Mouse OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer, including Lef1, Sp5, Ets2, Rnf43 and Dusp4. Surprisingly, we found that OPCs in lesions of hypoxic human neonatal white matter injury upregulated markers of high Wnt activity and lacked expression of APC. We also found that lack of Wnt repressor tone promoted permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack predisposing genetic mutation. |
Databáze: | OpenAIRE |
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