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
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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