Regulation of melanoma initiating cells by Hedgehog signaling and SOX2

Abstract

Background Recent reports suggest that within the heterogeneous population that constitutes a melanoma, certain cell types exhibit molecular and functional features similar to stem cells. These melanoma-initiating cells (MICs) have the ability of unlimited self-renewal, multilineage differentiation and the potential to initiate and maintain tumor growth [1]. Furthermore, MICs are believed to confer chemoresistance to conventional chemotherapeutic agents and newly developed molecularly-targeted drugs [2,3]. Therefore, defining the molecular and biochemical pathways that support MICs is of critical importance for the development of more efficient targeted therapies. We have previously shown that the HEDGEHOG (HH) signaling is required for melanoma growth [4] and for survival and expansion of MICs [5]. Here we investigate the mechanism by which inhibition of the HH signaling leads to a decrease of MIC stemness, addressing the role of the transcription factor SOX2.