[HTML][HTML] SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor

FM Kaplan, CH Kugel, N Dadpey, Y Shao… - Journal of Biological …, 2012 - ASBMB
ERK1/2 signaling is frequently dysregulated in tumors through BRAF mutation. Targeting
mutant BRAF with vemurafenib frequently elicits therapeutic responses; however, durable
effects are often limited by ERK1/2 pathway reactivation via poorly defined mechanisms. We
generated mutant BRAF V600E melanoma cells that exhibit resistance to PLX4720, the tool
compound for vemurafenib, that co-expressed mutant (Q61K) NRAS. In these BRAF
V600E/NRAS Q61K co-expressing cells, re-activation of the ERK1/2 pathway during …