11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma.

Fecha de publicación: 22/09/2020

Autores de INCLIVA

Ana Pilar Berbegall Beltrán

Autor
Rosa Noguera Salva

Autor

Participantes ajenos a INCLIVA

Siaw, Joachim Tetteh
Javanmardi, Niloufar
Van den Eynden, Jimmy
Lind, Dan Emil
Fransson, Susanne
Martinez-Monleon, Angela
Djos, Anna
Sjoberg, Rose-Marie
Ostensson, Malin
Caren, Helena
Troen, Gunhild
Beiske, Klaus
Lai, Wei-Yun
Kogner, Per
Palmer, Ruth H
Hallberg, Bengt
Martinsson, Tommy

Grupos y Plataformas de I+D+i

Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

Leading Researcher

Samuel Navarro Fos

Abstract

High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine "bridge signature" that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, highlighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.