Community Research and Development Information Service - CORDIS

FP7

ATOH1MEDULLO Result In Brief

Project ID: 294010
Funded under: FP7-PEOPLE
Country: France

The molecular basis of medulloblastoma

Normal organ development is usually controlled by the same mechanisms as cancer. A European study set out to identify the molecular players that become deregulated in brain cancer.
The molecular basis of medulloblastoma
During cerebellar development, several signalling pathways such as the Wnt or Sonic Hedgehog pathways play key roles in cell fate determination, axis formation, and patterning. Deregulation of these processes may lead to medulloblastoma (MB), the most common malignant paediatric brain tumour.

Depending on the affected pathway, there are four categories of MB. Group 1 is associated with mutations in the WNT pathway, group 2 shows a constitutive activation of Sonic Hedgehog signalling while the other two categories are not as well characterised. Existing therapies for MB have severe side effects and lead to a high mortality rate, highlighting the need for new drugs.

Towards this goal, scientists on the EU-funded ATOH1MEDULLO (Atoh1/Math1 regulation and function during cerebellar normal development and medulloblastoma) project proposed to decipher fundamental mechanisms related to the complex biology of MB.

Previous work by the project scientists had identified a central role for the bHLH transcription factor Atoh1 in tumour progression. During ATOH1MEDULLO, they envisioned the molecular pathways that regulate Atoh1 as potential new targets for therapeutic intervention.

They observed that Sonic Hedgehog regulated Atoh1 stability by preventing its degradation by the E3 ubiquitin ligase Huwe1. MB patients with lower Huwe1 expression exhibited poor prognosis indicating that the crosstalk between Sonic Hedgehog signalling and Atoh1 constitutes a potential target for MB treatment.

Collectively, the findings of the study further support the importance of the Sonic Hedgehog pathway in normal cerebellar development as well as a therapy axis for MB. Future studies to fully elucidate Atoh1 regulation have the potential to uncover more therapeutic targets.

Related information

Keywords

Medulloblastoma, sonic hedgehog, Atoh1, Huwe1, treatment
Record Number: 188679 / Last updated on: 2016-10-18
Domain: Biology, Medicine