OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells

@article{Bunt2012OTX2DA,
  title={OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells},
  author={Jens Bunt and Nancy E. Hasselt and Danny A Zwijnenburg and Mohamed Hamdi and Jan Koster and Rogier Versteeg and Marcel Kool},
  journal={International Journal of Cancer},
  year={2012},
  volume={131}
}
The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. To study the role OTX2 has in medulloblastoma we investigated the downstream pathway of OTX2. We generated D425 medulloblastoma cells in which endogenous OTX2 can be silenced by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a… Expand
An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate
TLDR
It is shown that OTX2 regulates PAX3 to induce neural de-differentiation and promote tumourigenesis in Group 3 medulloblastoma. Expand
OTX2 represses myogenic and neuronal differentiation in medulloblastoma cells.
TLDR
The discovery of RNA interference-mediated attenuation of OTX2 expression triggered myogenic and neuronal differentiation in vitro and prolonged the survival in an orthotopic medulloblastoma mouse model, illustrating the origin of muscle cells in medullomyoblastomas and the oncogenic mechanism of OTx2 as a repressor of diverse differentiating potential. Expand
Tumor and Stem Cell Biology OTX 2 Represses Myogenic and Neuronal Differentiation in Medulloblastoma Cells
The brain development transcription factor OTX2 is overexpressed and/or genomically amplified in most medulloblastomas, but the mechanistic basis for its contributions in this setting are notExpand
Aberrantly Expressed OTX Homeobox Genes Deregulate B-Cell Differentiation in Hodgkin Lymphoma
TLDR
Examination of expression and function of OTX homeobox genes which activate MSX1 transcription during embryonal development in the neural plate border region shows how reactivation of a specific embryonal gene regulatory network promotes disturbed B-cell differentiation in HL. Expand
OTX2 Activity at Distal Regulatory Elements Shapes the Chromatin Landscape of Group 3 Medulloblastoma.
TLDR
Using chromatin profiling, it is found that the transcription factor OTX2 acts as a pioneer factor and, in cooperation with NEUROD1, controls the Group 3 medulloblastoma active enhancer landscape. Expand
OTX2 expression contributes to proliferation and progression in Myc-amplified medulloblastoma.
TLDR
The interaction pathways and binding partners involved in OTX2 function, its usefulness as a molecular marker for risk stratification and prognosis, and the mechanism by which it drives tumor maintenance are defined. Expand
OTX2 exhibits cell-context-dependent effects on cellular and molecular properties of human embryonic neural precursors and medulloblastoma cells
TLDR
Human embryonic stem cell neural derivatives can be used to model the molecular and cellular properties of medulloblastoma and demonstrate a novel role for OTX2 in self-renewal and migration of hENs and MB cells and reveal a cell-context-dependent link between OTX1 and pluripotent genes. Expand
Aberrant Otx2 Expression Enhances Migration and Induces Ectopic Proliferation of Hindbrain Neuronal Progenitor Cells
TLDR
These studies implicate a role for Otx2 in altering the dynamics of neuronal progenitor cell proliferation in medulloblastoma precursor cells identified in animal models of Shh or Wnt group tumors. Expand
Characterization of a novel OTX2‐driven stem cell program in Group 3 and Group 4 medulloblastoma
TLDR
It is shown that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self‐renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo and that RHO signaling is contributing to the OTX2 KD phenotype. Expand
DMBX1 promotes tumor proliferation and regulates cell cycle progression via repressing OTX2-mediated transcription of p21 in lung adenocarcinoma cell.
TLDR
The study reveals that DMBX1 plays an oncogenic role in LUAD by repressing OTX2-mediated transcription of p21 and the results may provide new therapeutic targets for LUAD patients. Expand
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