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Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma

Kahn, Suzana A. (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Canc Ctr, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA
Wang, Xin (author)
Univ Toronto, Hosp Sick Children, Div Neurosurg, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 0A4, Canada
Nitta, Ryan T. (author)
Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA
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Gholamin, Sharareh (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Canc Ctr, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA
Theruvath, Johanna (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA
Hutter, Gregor (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA
Azad, Tej D. (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA
Wadi, Lina (author)
Ontario Inst Canc Res, Computat Biol Program, Toronto, ON M5G 0A3, Canada
Bolin, Sara, 1988- (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA
Ramaswamy, Vijay (author)
Univ Toronto, Hosp Sick Children, Div Neurosurg, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 0A4, Canada
Esparza, Rogelio (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA
Liu, Kun-Wei (author)
Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, 2880 Torrey Pines Scen Dr, La Jolla, CA 92037 USA
Edwards, Michael (author)
Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA
Johansson, Fredrik K., 1975- (author)
Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
Sahoo, Debashis (author)
Univ Calif San Diego, Dept Pediat, San Diego, CA 92093 USA;Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92093 USA
Li, Gordon (author)
Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA
Wechsler-Reya, Robert J. (author)
Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, 2880 Torrey Pines Scen Dr, La Jolla, CA 92037 USA
Reimand, Juri (author)
Ontario Inst Canc Res, Computat Biol Program, Toronto, ON M5G 0A3, Canada;Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada
Cho, Yoon-Jae (author)
Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA
Taylor, Michael D. (author)
Univ Toronto, Hosp Sick Children, Div Neurosurg, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 0A4, Canada
Weissman, Irving L. (author)
Stanford Univ, Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Canc Ctr, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA
Mitra, Siddhartha S. (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Canc Ctr, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA;Univ Colorado, Sch Med, Childrens Hosp Colorado, Dept Pediat, Room P18-4114,Res Complex 1 North MS 8302, Aurora, CO 80045 USA
Cheshier, Samuel H. (author)
Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Canc Ctr, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Neurosurg, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Ludwig Inst Canc Res, Sch Med, Stanford, CA 94305 USA;Univ Utah, Primary Childrens Hosp, Div Pediat Neurosurg, Dept Neurosurg, 100 North Mario Capecchi Dr Suite 3850, Salt Lake City, UT 84113 USA;Univ Utah, Huntsman Canc Inst, 100 North Mario Capecchi Dr Suite 3850, Salt Lake City, UT 84113 USA
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 (creator_code:org_t)
2018-10-08
2018
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
Related links:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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