PUBLICATION

Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness

Authors
Topczewska, J.M., Postovit, L.M., Margaryan, N.V., Sam, A., Hess, A.R., Wheaton, W.W., Nickoloff, B.J., Topczewski, J., and Hendrix, M.J.
ID
ZDB-PUB-060816-11
Date
2006
Source
Nature medicine   12(8): 925-932 (Journal)
Registered Authors
Sam, Anthony, Topczewska, Jolanta, Topczewski, Jacek
Keywords
none
MeSH Terms
  • Animals
  • Blastula/transplantation
  • Cell Line, Tumor
  • Embryo, Nonmammalian
  • Green Fluorescent Proteins/metabolism
  • Humans
  • Immunohistochemistry
  • Melanocytes/metabolism
  • Melanocytes/pathology
  • Melanoma/pathology*
  • Membrane Proteins/antagonists & inhibitors
  • Membrane Proteins/metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms/metabolism*
  • Oligonucleotides, Antisense/pharmacology
  • Signal Transduction*
  • Transplantation, Heterologous
  • Zebrafish/embryology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/metabolism*
PubMed
16892036 Full text @ Nat. Med.
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes