Polycomb group gene bMI1 controls invasion of medulloblastoma cells and inhibits BMP-regulated cell adhesion

Ashirwad Merve, Adrian M. Dubuc, Xinyu Zhang, Marc Remke, Patricia A. Baxter, Xiao Nan Li, Michael D. Taylor, Silvia Marino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: Medulloblastoma is the most common intracranial childhood malignancy and a genetically heterogeneous disease. Despite recent advances, current therapeutic approaches are still associated with high morbidity and mortality. Recent molecular profiling has suggested the stratification of medulloblastoma from one single disease into four distinct subgroups namely: WNT Group (best prognosis), SHH Group (intermediate prognosis), Group 3 (worst prognosis) and Group 4 (intermediate prognosis). BMI1 is a Polycomb group repressor complex gene overexpressed across medulloblastoma subgroups but most significantly in Group 4 tumours. Bone morphogenetic proteins are morphogens belonging to TGF-β superfamily of growth factors, known to inhibit medulloblastoma cell proliferation and induce apoptosis. Results: Here we demonstrate that human medulloblastoma of Group 4 characterised by the greatest overexpression of BMI1, also display deregulation of cell adhesion molecules. We show that BMI1 controls intraparenchymal invasion in a novel xenograft model of human MB of Group 4, while in vitro assays highlight that cell adhesion and motility are controlled by BMI1 in a BMP dependent manner. Conclusions: BMI1 controls MB cell migration and invasion through repression of the BMP pathway, raising the possibility that BMI1 could be used as a biomarker to identify groups of patients who may benefit from a treatment with BMP agonists.

Original languageEnglish (US)
Article number10
JournalActa Neuropathologica Communications
Volume2
Issue number1
DOIs
StatePublished - Jan 27 2014

Keywords

  • BMI1
  • BMP
  • Cell adhesion
  • Cell motility
  • Medulloblastoma

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Polycomb group gene bMI1 controls invasion of medulloblastoma cells and inhibits BMP-regulated cell adhesion'. Together they form a unique fingerprint.

Cite this