DDX3X Suppresses the Susceptibility of Hindbrain Lineages to Medulloblastoma.

Dev Cell

CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK; Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. Electronic address:

Published: August 2020

DEAD-Box Helicase 3 X-Linked (DDX3X) is frequently mutated in the Wingless (WNT) and Sonic hedghog (SHH) subtypes of medulloblastoma-the commonest malignant childhood brain tumor, but whether DDX3X functions as a medulloblastoma oncogene or tumor suppressor gene is not known. Here, we show that Ddx3x regulates hindbrain patterning and development by controlling Hox gene expression and cell stress signaling. In mice predisposed to Wnt- or Shh medulloblastoma, Ddx3x sensed oncogenic stress and suppressed tumor formation. WNT and SHH medulloblastomas normally arise only in the lower and upper rhombic lips, respectively. Deletion of Ddx3x removed this lineage restriction, enabling both medulloblastoma subtypes to arise in either germinal zone. Thus, DDX3X is a medulloblastoma tumor suppressor that regulates hindbrain development and restricts the competence of cell lineages to form medulloblastoma subtypes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483908PMC
http://dx.doi.org/10.1016/j.devcel.2020.05.027DOI Listing

Publication Analysis

Top Keywords

tumor suppressor
8
regulates hindbrain
8
medulloblastoma subtypes
8
ddx3x
7
medulloblastoma
6
ddx3x suppresses
4
suppresses susceptibility
4
susceptibility hindbrain
4
hindbrain lineages
4
lineages medulloblastoma
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!