AI Article Synopsis
- ADGRs are a group of 33 human proteins that play a role in cell interactions, and BAI1, encoded by the ADGRB1 gene, is important in brain development.
- In medulloblastomas, the ADGRB1 gene is silenced due to DNA methylation through the protein MBD2, leading to increased cell growth and tumor progression in mice.
- The loss of BAI1 results in lower p53 protein levels, but restoring the BAI1/p53 signaling pathway can slow down medulloblastoma growth, indicating BAI1's crucial role in cancer development.
Article Abstract
Adhesion G protein-coupled receptors (ADGRs) encompass 33 human transmembrane proteins with long N termini involved in cell-cell and cell-matrix interactions. We show the ADGRB1 gene, which encodes Brain-specific angiogenesis inhibitor 1 (BAI1), is epigenetically silenced in medulloblastomas (MBs) through a methyl-CpG binding protein MBD2-dependent mechanism. Knockout of Adgrb1 in mice augments proliferation of cerebellar granule neuron precursors, and leads to accelerated tumor growth in the Ptch1 transgenic MB mouse model. BAI1 prevents Mdm2-mediated p53 polyubiquitination, and its loss substantially reduces p53 levels. Reactivation of BAI1/p53 signaling axis by a brain-permeable MBD2 pathway inhibitor suppresses MB growth in vivo. Altogether, our data define BAI1's physiological role in tumorigenesis and directly couple an ADGR to cancer formation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002773 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2018.05.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The regulation of BAI1 in astrocytes through the STAT3/EZH2 axis relieves neuronal apoptosis in rats with Alzheimer's disease.
Brain Res
September 2024
Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang 310005, China. Electronic address:
Alzheimer's disease (AD) is a common neurodegenerative disease. Previous studies have identified the critical role of astrocytes in the progression of AD. The focus of this study revolves around clarifying the regulatory mechanism of the STAT3/EZH2/BAI1 axis in astrocytes in AD.
View Article and Find Full Text PDFEZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain.
Cells
March 2023
Department of Basic Sciences, California Northstate University College of Medicine, Elk Grove, CA 95757, USA.
Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis of neuropathic pain by modulating the production of proinflammatory cytokines and chemokines. In this review, we summarize recent advances in this research area. EZH2 is a subunit of polycomb repressive complex 2 (PRC2), which primarily serves as a histone methyltransferase to catalyze methylation of histone 3 on lysine 27 (H3K27), ultimately resulting in transcriptional repression.
View Article and Find Full Text PDFReprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling.
Cell Mol Immunol
December 2022
Department of Physiology, College of Medicine, Ewha Womans University, Seoul, 07804, Korea.
The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis. Cancer-associated fibroblasts (CAFs) play a crucial role in promoting these events through paracrine communication. Here, we demonstrate that conditioned medium (CM) from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs.
View Article and Find Full Text PDFMice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development.
Exp Neurol
May 2022
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address:
The adhesion G protein-coupled receptor BAI1/ADGRB1 plays an important role in suppressing angiogenesis, mediating phagocytosis, and acting as a brain tumor suppressor. BAI1 is also a critical regulator of dendritic spine and excitatory synapse development and interacts with several autism-relevant proteins. However, little is known about the relationship between altered BAI1 function and clinically relevant phenotypes.
View Article and Find Full Text PDFOpuntia ficus-indica Extract and Isorhamnetin-3-O-Glucosyl-Rhamnoside Diminish Tumor Growth of Colon Cancer Cells Xenografted in Immune-Suppressed Mice through the Activation of Apoptosis Intrinsic Pathway.
Plant Foods Hum Nutr
December 2021
Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología-FEMSA, Av. Eugenio Garza Sada 2501 Sur, C.P. 64849, Monterrey, N.L., Mexico.
This study aimed to evaluate the effects of Opuntia ficus-indica extract (OFI-E) and its glycoside isorhamnetin-3-O-glucosyl-rhamnoside (IGR) on the growth of human colorectal adenocarcinoma cells and in a xenografted-immunosuppressed mice model. The IC values of OFI-E and IGR on colon cancer cells (HT-29 RFP) were determinate, as well as their effects on the cell cycle and apoptosis induction. OFI-E and IGR produced an increased in apoptosis induction, ROS production and a G0/G1 cell cycle arrest.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!