Using intravital imaging to detect ERK activation in melanoma cells, Hirata et al. showed that vemurafenib can activate and remodel CAFs to generate an extracellular matrix rich in fibronectin and collagen, which can stimulate β1-integrin/focal adhesion kinase/SRC signaling in melanoma cells, resulting in MAPK reactivation. This evidence concerns the gene FN1 and melanoma.