| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
1 Signal Transduction Team, The Institute for Cancer Research, Cancer Research UK Centre of Cell and Molecular Biology, London, United Kingdom, 2 Gene and Oncogene Targeting Team, Cancer Research UK Centre for Cancer Therapeutics, Sutton, United Kingdom; and 3 Departments of Dermatology and Pathology and Comprehensive Cancer, University of California San Francisco, San Francisco, California
Requests for reprints: Richard Marais, Signal Transduction Team, The Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, United Kingdom. Phone: 44-20-7878-3856; Fax: 44-20-7878-3856; E-mail: richard.marais{at}icr.ac.uk.
Melanocytes require the RAS/RAF/MEK/ERK and the cyclic AMP (cAMP) signaling pathways to maintain the fine balance between proliferation and differentiation. We have investigated how cross-talk between these pathways affects melanoma progression. We show that cAMP suppresses CRAF activity in melanocytes and that this is essential to suppress the oncogenic potential of CRAF in these cells. As a consequence, BRAF alone is responsible for signaling to MEK. However, when RAS is mutated in melanoma, the cells switch their signaling from BRAF to CRAF. This switch is accompanied by dysregulated cAMP signaling, a step that is necessary to allow CRAF to signal to MEK. Thus, a fundamental switch in RAF isoform usage occurs when RAS is mutated in melanoma, and this occurs in the context of disrupted cAMP signaling. These data have important implications for the development of therapeutic strategies to treat this life-threatening disease. (Cancer Res 2006; 66(19): 9483-91)
This article has been cited by other articles:
|
|
 |
|
  C. Anastasaki, A. L. Estep, R. Marais, K. A. Rauen, and E. E. Patton Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors Hum. Mol. Genet., July 15, 2009; 18(14): 2543 - 2554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S.M. Smalley, K. L. Nathanson, and K. T. Flaherty Genetic Subgrouping of Melanoma Reveals New Opportunities for Targeted Therapy Cancer Res., April 15, 2009; 69(8): 3241 - 3244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Montagut, S. V. Sharma, T. Shioda, U. McDermott, M. Ulman, L. E. Ulkus, D. Dias-Santagata, H. Stubbs, D. Y. Lee, A. Singh, et al. Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma Cancer Res., June 15, 2008; 68(12): 4853 - 4861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Muller, M. Obeyesekere, G. B. Mills, and P. T. Ram Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R FASEB J, May 1, 2008; 22(5): 1393 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lehnerdt, P. Franz, A. Zaqoul, K. J. Schmitz, S. Grehl, S. Lang, K. W. Schmid, W. Siffert, K. Jahnke, and U. H. Frey Overall and Relapse-Free Survival in Oropharyngeal and Hypopharyngeal Squamous Cell Carcinoma Are Associated with Genotypes of T393C Polymorphism of the GNAS1 Gene Clin. Cancer Res., March 15, 2008; 14(6): 1753 - 1758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Marais BRAF Signaling in Cancer: Biology and Therapeutic Opportunities Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 167 - 174. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
