These authors contributed equally.
A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status
Article first published online: 12 JAN 2011
© 2011 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 24, Issue 2, pages 326–333, April 2011
How to Cite
Zipser, M. C., Eichhoff, O. M., Widmer, D. S., Schlegel, N. C., Schoenewolf, N. L., Stuart, D., Liu, W., Gardner, H., Smith, P. D., Nuciforo, P., Dummer, R. and Hoek, K. S. (2011), A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status. Pigment Cell & Melanoma Research, 24: 326–333. doi: 10.1111/j.1755-148X.2010.00823.x
- Issue published online: 10 MAR 2011
- Article first published online: 12 JAN 2011
- Accepted manuscript online: 22 DEC 2010 12:40PM EST
- PUBLICATION DATA Received 6 August 2010, revised and accepted for publication 17 December 2010, published online 22 December 2010
- phenotype switching;
- MAPK inhibition
Oncogenic mutations within the MAPK pathway are frequent in melanoma, and targeting of MAPK signaling has yielded spectacular responses in a significant number of patients that last for several months before relapsing. We investigated the effects of two different inhibitors of MAPK signaling in proliferative and invasive melanoma cell cultures with various mutations in the MAPK pathway. Proliferative melanoma cells were more susceptible to pathway inhibition than invasive phenotype cells, irrespective of BRAF mutation status, while invasive phenotype cell response was dependent on BRAF mutation status. Critically, MAPK pathway inhibition of proliferative phenotype cells resulted in acquisition of invasive phenotype characteristics. These results show that melanoma cell phenotype is an important factor in MAPK pathway inhibition response. This suggests that while current therapeutic strategies target proliferative melanoma cells, future approaches should also account for the invasive phenotype population.