Activated ALK signals through the ERK-ETV5-RET pathway to drive neuroblastoma oncogenesis.

ABSTRACT: Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alk^mut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/Ret^M919T tumors exhibit histological features and expression profiles close to MYCN/Alk^mut tumors. We show that RET transcript levels decrease precedes RET protein levels decrease upon ALK inhibition in neuroblastoma cell lines. Etv5 was identified as a candidate transcription factor regulating Ret expression from murine MYCN/Alk

SUBMITTER: Lopez-Delisle L 

PROVIDER: S-EPMC6168456 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature