The oncogenic epidermal growth factor receptor variant Xiphophorus melanoma receptor kinase induces motility in melanocytes by modulation of focal adhesions.
One of the most prominent features of malignant melanoma is the fast generation of metastasizing cells, resulting in the poor prognosis of patients with this tumor type. For this process, cells must gain the ability to migrate. The oncogenic receptor Xmrk (Xiphophorus melanoma receptor kinase) from the Xiphophorus melanoma system is a mutationally activated version of the epidermal growth factor receptor that induces the malignant transformation of pigment cells. Here, we show that the activation of Xmrk leads to a clear increase of pigment cell motility in a fyn-dependent manner. Stimulation of Xmrk induces its interaction with the focal adhesion kinase (FAK) and the interaction of active, receptor-bound fyn with FAK. This results in changes in FAK activity and induces the modulation of stress fibers and focal adhesions. Overexpression of dominant-negative FAK shows that the activity of innate FAK and a receptor-induced focal adhesion turnover are a prerequisite for pigment cell migration. Our findings show that in our system, Xmrk is sufficient for the induction of pigment cell motility and underlines a role of the src family protein tyrosine kinase fyn in melanoma development and progression.
Department of Physiological Chemistry I, Biocenter, University of Wuerzburg, Wuerzburg, Germany. svenja.meierjohann@biozentrum.uni-wuerzburg.de
Svenja
S
Meierjohann
Elisabeth
E
Wende
Anita
A
Kraiss
Claudia
C
Wellbrock
Manfred
M
Schartl
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003532:Cyprinodontiformes; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
D029941:Fish Proteins; D020794:Receptor Protein-Tyrosine Kinases; C077101:Xmrk protein, Xiphophorus; D051416:Focal Adhesion Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn