The transcription factor Cux1 in cerebellar granule cell development and medulloblastoma pathogenesis
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The transcription factor Cux1 in cerebellar granule cell development and medulloblastoma pathogenesis. / Topka, Sabine; Glassmann, Alexander; Weisheit, Gunnar; Schüller, Ulrich; Schilling, Karl.
in: CEREBELLUM, Jahrgang 13, Nr. 6, 12.2014, S. 698-712.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The transcription factor Cux1 in cerebellar granule cell development and medulloblastoma pathogenesis
AU - Topka, Sabine
AU - Glassmann, Alexander
AU - Weisheit, Gunnar
AU - Schüller, Ulrich
AU - Schilling, Karl
PY - 2014/12
Y1 - 2014/12
N2 - Cux1, also known as Cutl1, CDP or Cut is a homeodomain transcription factor implicated in the regulation of normal and oncogenic development in diverse peripheral tissues and organs. We studied the expression and functional role of Cux1 in cerebellar granule cells and medulloblastoma. Cux1 is robustly expressed in proliferating granule cell precursors and in postmitotic, migrating granule cells. Expression is lost as postmigratory granule cells mature. Moreover, Cux1 is also strongly expressed in a well-established mouse model of medulloblastoma. In contrast, expression of CUX1 in human medulloblastoma tissue samples is lower than in normal fetal cerebellum. In these tumors, CUX1 expression tightly correlates with a set of genes which, when mapped on a global protein-protein interaction dataset, yields a tight network that constitutes a cell cycle control signature and may be related to p53 and the DNA damage response pathway. Antisense-mediated reduction of CUX1 levels in two human medulloblastoma cell lines led to a decrease in proliferation and altered motility. The developmental expression of Cux1 in the cerebellum and its action in cell lines support a role in granule cell and medulloblastoma proliferation. Its expression in human medulloblastoma shifts that perspective, suggesting that CUX1 is part of a network involved in cell cycle control and maintenance of DNA integrity. The constituents of this network may be rational targets to therapeutically approach medulloblastomas.
AB - Cux1, also known as Cutl1, CDP or Cut is a homeodomain transcription factor implicated in the regulation of normal and oncogenic development in diverse peripheral tissues and organs. We studied the expression and functional role of Cux1 in cerebellar granule cells and medulloblastoma. Cux1 is robustly expressed in proliferating granule cell precursors and in postmitotic, migrating granule cells. Expression is lost as postmigratory granule cells mature. Moreover, Cux1 is also strongly expressed in a well-established mouse model of medulloblastoma. In contrast, expression of CUX1 in human medulloblastoma tissue samples is lower than in normal fetal cerebellum. In these tumors, CUX1 expression tightly correlates with a set of genes which, when mapped on a global protein-protein interaction dataset, yields a tight network that constitutes a cell cycle control signature and may be related to p53 and the DNA damage response pathway. Antisense-mediated reduction of CUX1 levels in two human medulloblastoma cell lines led to a decrease in proliferation and altered motility. The developmental expression of Cux1 in the cerebellum and its action in cell lines support a role in granule cell and medulloblastoma proliferation. Its expression in human medulloblastoma shifts that perspective, suggesting that CUX1 is part of a network involved in cell cycle control and maintenance of DNA integrity. The constituents of this network may be rational targets to therapeutically approach medulloblastomas.
KW - Animals
KW - Apoptosis
KW - Cell Line, Tumor
KW - Cell Movement
KW - Cerebellum
KW - Disease Models, Animal
KW - Homeodomain Proteins
KW - Humans
KW - Medulloblastoma
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Neural Stem Cells
KW - Neurogenesis
KW - Neurons
KW - Nuclear Proteins
KW - Repressor Proteins
KW - Journal Article
U2 - 10.1007/s12311-014-0588-x
DO - 10.1007/s12311-014-0588-x
M3 - SCORING: Journal article
C2 - 25096634
VL - 13
SP - 698
EP - 712
JO - CEREBELLUM
JF - CEREBELLUM
SN - 1473-4222
IS - 6
ER -