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.