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Mol Cancer Res. 2011 Jun;9(6):801-12. doi: 10.1158/1541-7786.MCR-10-0512. Epub 2011 Apr 26.

Phosphoproteomic screen identifies potential therapeutic targets in melanoma.

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1
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

Therapies directed against receptor tyrosine kinases are effective in many cancer subtypes, including lung and breast cancer. We used a phosphoproteomic platform to identify active receptor tyrosine kinases that might represent therapeutic targets in a panel of 25 melanoma cell strains. We detected activated receptors including TYRO3, AXL, MERTK, EPHB2, MET, IGF1R, EGFR, KIT, HER3, and HER4. Statistical analysis of receptor tyrosine kinase activation as well as ligand and receptor expression indicates that some receptors, such as FGFR3, may be activated via autocrine circuits. Short hairpin RNA knockdown targeting three of the active kinases identified in the screen, AXL, HER3, and IGF1R, inhibited the proliferation of melanoma cells and knockdown of active AXL also reduced melanoma cell migration. The changes in cellular phenotype observed on AXL knockdown seem to be modulated via the STAT3 signaling pathway, whereas the IGF1R-dependent alterations seem to be regulated by the AKT signaling pathway. Ultimately, this study identifies several novel targets for therapeutic intervention in melanoma.

PMID:
21521745
PMCID:
PMC3117976
DOI:
10.1158/1541-7786.MCR-10-0512
[Indexed for MEDLINE]
Free PMC Article
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