IRX2 and NPTX1 differential regulation of β-catenin underlies MEK-mediated proliferation in human neuroglial cells
Year: 2025
Type: preprint
Abstract: The two major genomic alterations in pediatric pilocytic astrocytoma (PA) are NF1 loss and KIAA1549:BRAF rearrangement. Although these molecular changes result in increased MEK activity and tumor growth, it is not clear exactly how MEK controls human neuroglial cell proliferation. Leveraging human-induced pluripotent stem cells harboring these PA-associated alterations, we used a combination of genetic and pharmacological approaches to demonstrate that MEK-regulated cell growth is mediated by β-catenin through independent mechanisms involving IRX2 control of CTNNB1 transcription and NPTX1 stabilization of β-catenin protein levels. These results provide new mechanistic insights into MEK regulation of human brain cell function.
Source: Genes & Development
Institution: Washington University in St. Louis
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: Gilbert Family Foundation, National Cancer Center, National Institutes of Health, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, National Center for Advancing Translational Sciences
OpenAlex ID: W4409487594