title: Embryonic signaling in melanoma: potential for diagnosis and therapy.
abstract: As the frequency of melanoma diagnosis increases, current treatment strategies are still struggling to significantly impact patient survival. Some promise has been shown in treating certain melanomas by targeting activated signaling pathways resulting from specific mutations in proteins, such as BRAF and NRAS. Recently, the identification of embryonic signaling pathways in melanoma has helped us better understand certain biological characteristics, such as cellular heterogeneity and phenotypic plasticity, and has provided novel insight pertinent to diagnosis and therapy. For instance, our studies have shown that the TGF-β family member, Nodal, is expressed in melanoma and is responsible, at least in part, for tumor cell plasticity and aggressiveness. Since the majority of normal adult tissues do not express Nodal, we reason that this embryonic morphogen could be used to identify and target aggressive melanoma cells. We have also identified that molecular cross-talk between the Notch and Nodal pathways may represent a mechanism responsible for the overexpression of Nodal in melanoma. Further exploitation of the relationship between embryonic signaling pathways and cancer pathogenesis could lead to novel approaches for diagnosis and therapy in cancers, such as melanoma.
authors.affiliation: Children’s Memorial Research Center, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 2300 Children’s Plaza, Box 222, Chicago, IL 60614, USA. lstrizzi@childrensmemorial.org
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Hardy
authors.forename: Gina T
authors.initials: GT
authors.lastname: Kirsammer
authors.forename: Pedram
authors.initials: P
authors.lastname: Gerami
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D045744:Cell Line, Tumor; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D008954:Models, Biological; D055457:Nodal Protein / Q000378:metabolism*; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology
chemical_list: C526007:NODAL protein, human; D055457:Nodal Protein; D051880:Receptors, Notch