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|Title:||Kinase-dead BRAF and oncongenic RAS cooperate to drive tumour progression through CRAF|
|Authors:||Heidorn, S. J.|
Niculescu Duvas, I.
Reis Filho, J. S.
Springer, C. J.
|Publisher:||Elsevier (Cell Press)|
|Citation:||Cell, 2010, 140 (2), pp. 209-221|
|Abstract:||We describe a mechanism of tumorigenesis mediated by kinase-dead BRAF in the presence of oncogenic RAS. We show that drugs that selectively inhibit BRAF drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK–ERK signaling. This does not occur when oncogenic BRAF is inhibited, demonstrating that BRAF inhibition per se does not drive pathway activation; it only occurs when BRAF is inhibited in the presence of oncogenic RAS. Kinase-dead BRAF mimics the effects of the BRAF-selective drugs and kinase-dead Braf and oncogenic Ras cooperate to induce melanoma in mice. Our data reveal another paradigm of BRAF-mediated signaling that promotes tumor progression. They highlight the importance of understanding pathway signaling in clinical practice and of genotyping tumors prior to administering BRAF-selective drugs, to identify patients who are likely to respond and also to identify patients who may experience adverse effects.|
|Rights:||Open access under CC BY license|
|Description:||Supplemental Information includes Extended Experimental Procedures, four figures, and three tables and can be found with this article online at doi: 10.1016/j.cell.2009.12.040.|
|Appears in Collections:||Published Articles, Dept. of Cancer Studies and Molecular Medicine|
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