@article{2cfc2fc7a5894efa93ed3864af856c06,
title = "Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma",
abstract = "Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through the activation of TWIST1. NOTCH1 expression and activity are directly related to medulloblastoma metastasis and decreased survival rate of tumor-bearing mice. Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3 medulloblastoma metastasis and self-renewal, supporting the development of therapies targeting this pathway.",
author = "Kahn, {Suzana A.} and Xin Wang and Nitta, {Ryan T.} and Sharareh Gholamin and Johanna Theruvath and Gregor Hutter and Azad, {Tej D.} and Lina Wadi and Sara Bolin and Vijay Ramaswamy and Rogelio Esparza and Liu, {Kun Wei} and Michael Edwards and Swartling, {Fredrik J.} and Debashis Sahoo and Gordon Li and Wechsler-Reya, {Robert J.} and J{\"u}ri Reimand and Cho, {Yoon Jae} and Taylor, {Michael D.} and Weissman, {Irving L.} and Mitra, {Siddhartha S.} and Cheshier, {Samuel H.}",
note = "Funding Information: This work was supported by the Pew Latin American Fellowship (S.A.K.), Price Family Charitable Fund, Center for Children{\textquoteright}s Brain Tumors (S.G, S.S.M., and S.H.C.), American Brain Tumor Foundation (S.H.C.), Matthew Larson Foundation for Pediatric Brain Tumors (S.A.K. and S.H.C.), Virginia and D.K. Ludwig Fund for Cancer Research (I.L.W. and S.H.C.), Lucile Packard Foundation for Children{\textquoteright}s Health, Child Health Research Institute at Stanford Tashia and John Morgridge Faculty Scholarship in Pediatric Translational Medicine NIH-NCATS-CTSA UL1 TR001085 (S.H.C.). German Cancer Aid (Deutsche Krebshilfe) P-91650709 (J.T.). Ty Louis Campbell Foundation St. Baldrick{\textquoteright}s Foundation Award (S.HC.) Gifts from Kathryn S.R. Lowrey, George Landegger, Rider and Victoria McDowell, Charles Comey and Judith Huang, and Colin and Jenna Fisher (S.H.C.). Canadian NSERC Discovery Grant RGPIN-2016-06485 (L.W). Operating Grant 21089 of the Cancer Research Society of Canada (J.R.). R01 NS096368-02 (R.J.W.-R.).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-06564-9",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}