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Role of LIM and SH3 Protein 1 (LASP1) in the Metastatic Dissemination of Medulloblastoma

Medulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of interme...

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Main Authors: Tränka, Christopher (Author) , Remke, Marc (Author) , Korshunov, Andrey (Author) , Bender, Sebastian (Author) , Hielscher, Thomas (Author) , Northcott, Paul A. (Author) , Witt, Hendrik (Author) , Ryzhova, Marina (Author) , Felsberg, Jörg (Author) , Benner, Axel (Author) , Riester, Stephanie (Author) , Scheurlen, Wolfram (Author) , Grünewald, Thomas G. P. (Author) , Deimling, Andreas von (Author) , Kulozik, Andreas (Author) , Reifenberger, Guido (Author) , Taylor, Michael D. (Author) , Lichter, Peter (Author) , Butt, Elke (Author) , Pfister, Stefan (Author)
Format: Article (Journal)
Language:English
Published: October 13 2010
In: Cancer research
Year: 2010, Volume: 70, Issue: 20, Pages: 8003-8014
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-10-0592
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/0008-5472.CAN-10-0592
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Author Notes:Christopher Traenka, Marc Remke, Andrey Korshunov, Sebastian Bender, Thomas Hielscher, Paul A. Northcott, Hendrik Witt, Marina Ryzhova, Jörg Felsberg, Axel Benner, Stephanie Riester, Wolfram Scheurlen, Thomas G.P. Grunewald, Andreas von Deimling, Andreas E. Kulozik, Guido Reifenberger, Michael D. Taylor, Peter Lichter, Elke Butt, Stefan M. Pfister
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Summary:Medulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk medulloblastoma. Through mRNA expression profiling, we identified LIM and SH3 protein 1 (LASP1) as one of the most upregulated genes on chromosome 17q in tumors with 17q gain. In an independent validation cohort of 101 medulloblastoma samples, the abundance of LASP1 mRNA was significantly associated with 17q gain, metastatic dissemination, and unfavorable outcome. LASP1 protein expression was analyzed by immunohistochemistry in a large cohort of patients (n = 207), and high protein expression levels were found to be strongly correlated with 17q gain, metastatic dissemination, and inferior overall and progression-free survival. In vitro experiments in medulloblastoma cell lines showed a strong reduction of cell migration, increased adhesion, and decreased proliferation upon LASP1 knockdown by small interfering RNA-mediated silencing, further indicating a functional role for LASP1 in the progression and metastatic dissemination of medulloblastoma. Cancer Res; 70(20); 8003-14. ©2010 AACR.
Item Description:Gesehen am 22.12.2023
Physical Description:Online Resource
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-10-0592

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