Melanoma, Genetically Engineered Mouse Models, Stem Cells
The goal of our research is to determine molecular mechanisms underlying melanoma initiation, growth, and metastasis formation, with a particular focus on embryonic programs reactivated during tumorigenesis.
Tumor cells conceivably share properties with normal cells of the tissue, from which the tumor derives. Melanoma arise from the pigment cell lineage that originates during embryonic development from neural crest stem cells (NCSCs). Our lab has demonstrated that multipotent cells with NCSC properties can be isolated from both human and mouse melanoma biopsies. Intriguingly, interfering with features of normal NCSCs influences tumor growth and invasiveness both in genetic melanoma mouse models in vivo and in human melanoma cells. For instance, a transcription factor signature active in NCSCs also appears to regulate ‘stemness’ properties and invasiveness in melanoma, and signaling pathways normally regulating NCSC fates control melanoma progression. Likewise, epigenetic and metabolic control mechanisms important for proper neural crest development are functionally involved in melanoma progression in vivo. Finally, there is increasing evidence that melanoma cells in response to targeted therapy and immunotherapy acquire a NCSC-like state associated with increased resistance. Thus, our research on stem cells during embryonic development provides insights into the biology of melanoma that might ultimately be relevant for treatment.Publications