Nature Medicine
- 12, 925 - 932 (2006)
Published online: 30 July 2006; | doi:10.1038/nm1448
Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressivenessJolanta M Topczewska1, 4, Lynne-Marie Postovit2, 4, Naira V Margaryan2, Anthony Sam1, Angela R Hess2, William W Wheaton2, Brian J Nickoloff3, Jacek Topczewski1 & Mary J C Hendrix21
Program in Developmental Biology, Children's Memorial Research Center, Feinberg School of Medicine Northwestern University, 2300 Children's Plaza, Box 222, Chicago Illinois, 60614, USA. 2
Program in Cancer Biology and Epigenomics, Children's Memorial Research Center, Feinberg School of Medicine Northwestern University, 2300 Children's Plaza, Box 222, Chicago Illinois, 60614, USA. 3
Department of Pathology, Loyola University Medical Center, Cardinal Bernardin Cancer Center, 2160 S. First Avenue, Building 112, Room 301, Maywood, Illinois 60153, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Mary J C Hendrix mjchendrix@childrensmemorial.org Bidirectional cellular communication is integral to both cancer progression and embryological development. In addition, aggressive tumor cells are phenotypically plastic, sharing many properties with embryonic cells. Owing to the similarities between these two types of cells, the developing zebrafish can be used as a biosensor for tumor-derived signals. Using this system, we show that aggressive melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can induce ectopic formation of the embryonic axis. We further show that Nodal is present in human metastatic tumors, but not in normal skin, and thus may be involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma cell invasiveness, colony formation and tumorigenicity. Nodal inhibition also promotes the reversion of melanoma cells toward a melanocytic phenotype. These data suggest that Nodal signaling has a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating tumor progression.
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