MYCN and MYC-regulated stem cell markers as therapeutic targets in neuroblastoma

Specific pathways that control crucial steps during embryonic development are often inappropriately reactivated during tumorigenesis. In addition cancer cells seem to take advantage of cellular principles inherent to normal stem cells, particularly the abilities to self-renew and differentiate into multiple cell types. Cancer stem cells (tumor-initiating cells) are believed to persist in tumors as a distinct population that likely causes disease relapse. Members of the MYC transcription factor family, in particular MYC and MYCN, are among very few genes that have the ability to restore stem cell potential in differentiated cells. Thus, deregulated MYC or MYCN protein functions may confer stem cell potential to cancer cells, trigger relentless tumor growth and high rate of tumor relapse. However, the target genes and the molecular mechanisms by which deregulated MYC proteins mediate these functions are still elusive. We are using inducible overexpression and knowdown in vitro systems that allow the regulation of MYCN and MYC functions in NB cells. Selective knockdown of MYCN/MYC target genes is currently performed to functionally dissect the MYCN/MYC pathway in NB cells.