| First Author | Zhu D | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 6 | Pages | 1004-1016.e5 |
| PubMed ID | 29894688 | Mgi Jnum | J:262547 |
| Mgi Id | MGI:6162285 | Doi | 10.1016/j.ccell.2018.05.006 |
| Citation | Zhu D, et al. (2018) BAI1 Suppresses Medulloblastoma Formation by Protecting p53 from Mdm2-Mediated Degradation. Cancer Cell 33(6):1004-1016.e5 |
| abstractText | 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. |
