Fig. 4

Pathway analysis of BRAF kinase inhibitor resistance shows alternative activation of MAPK targets and pigmentation. a Schematic representation of regulatory network involving drug inhibition and non-genomic selection for differential expression of driver genes that can circumvent suppressed signaling. b Deregulation of MAPK signaling with RNA-Seq data is mapped in red and blue for differential upregulation and downregulation, respectively. c Modulation of TGFB signaling leads to downregulation of dual specific phosphatases, which are required to switch MAPK signaling off. d Interconnectedness between G-protein signaling and melanogenesis. Alternative activation of melanoma pathways leads to increased eumelanin synthesis and mitogenic survival. Photograph of cell pellets of melanoma cell models and detected melanin. Left shows SK-MEL-28 melanoma cell line, middle and right shows two different SK-MEL-28-BRAFi-resistant melanoma cell lines with elevated melanin production