Lineage-restricted sympathoadrenal progenitors confer neuroblastoma origin and its tumorigenicity.

Lineage-restricted sympathoadrenal progenitors confer neuroblastoma origin and its tumorigenicity. Oncotarget. 2020 Jun 16;11(24):2357-2371 Authors: Yang CL, Serra-Roma A, Gualandi M, Bodmer N, Niggli F, Schulte JH, Bode PK, Shakhova O Abstract Neuroblastoma (NB) is the most common cancer in infants and it accounts for six percent of all pediatric malignancies. There are several hypotheses proposed on the origins of NB. While there is little genetic evidence to support this, the prevailing model is that NB originates from neural crest stem cells (NCSCs). Utilizing in vivo mouse models, we demonstrate that targeting MYCN oncogene to NCSCs causes perinatal lethality. During sympathoadrenal (SA) lineage development, SOX transcriptional factors drive the transition from NCSCs to lineage-specific progenitors, characterized by the sequential activation of Sox9/Sox10/Sox4/Sox11 genes. We find the NCSCs factor SOX10 is not expressed in neuroblasts, but rather restricted to the Schwannian stroma and is associated with a good prognosis. On the other hand, SOX9 expression in NB cells was associated with several key biological processes including migration, invasion and differentiation. Moreover, manipulating SOX9 gene predominantly affects lineage-restricted SA progenitors. Our findings highlight a unique molecular SOX signature associated with NB that is highly reminiscent of SA progenitor transcriptional program during embryonic development, ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research