As the upstream of IL-6, epiregulin-induced CAF activation promote EMT by activating IL-6/JAK2/STAT3 signaling axis, which could be inhibited by a JAK2 inhibitor (AG490).235 Intriguingly, the migration of melanoma cells was dependent on GP130-IL6ST/JAK1-ROCK signaling; however, although it was not necessary in cancer cells, this signaling pathway was required for CAF-induced ECM remodeling to promote the invasion of squamous cell carcinoma (SCC),237 indicating that the targeted therapy of JAK/STAT signaling pathway for SCC invasion might not be the epithelium but CAFs. This evidence concerns the gene IL6ST and melanoma.