Ligand-independent EPHA2 signaling drives the adoption of a targeted therapy-mediated metastatic melanoma phenotype.

@article{Paraiso2015LigandindependentES,
  title={Ligand-independent EPHA2 signaling drives the adoption of a targeted therapy-mediated metastatic melanoma phenotype.},
  author={Kim H. T. Paraiso and Meghna Das Thakur and Bin Fang and John Matthew Koomen and Inna V. Fedorenko and Jobin K. John and Hensin Tsao and Keith T Flaherty and Vernon K. Sondak and Jane L Messina and Elena B Pasquale and Alejandro Villagra and Ub. Narasinga Rao and John Munn Kirkwood and Friedegund Meier and Sarah Sloot and Geoffrey Thomas Gibney and Darrin D. Stuart and Hussein Tawbi and Keiran S. M. Smalley},
  journal={Cancer discovery},
  year={2015},
  volume={5 3},
  pages={
          264-73
        }
}
UNLABELLED Many patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here, we used mass spectrometry-based phosphoproteomic screening to uncover ligand-independent EPHA2 signaling as an adaptation to BRAF inhibitor therapy that led to the adoption of a metastatic phenotype. The EPHA2-mediated invasion was AKT-dependent and readily reversible upon removal of the drug as well as through PI3K and AKT inhibition… CONTINUE READING

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References

Publications referenced by this paper.
SHOWING 1-10 OF 28 REFERENCES

Hypoxiainduced pathological angiogenesis mediates tumor cell dissemination, invasion, and Research

SL Lee, P Rouhi, +3 authors G Hauptmann
  • on June
  • 2014