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. Author manuscript; available in PMC: 2021 Jun 1.
Published in final edited form as: Oncogene. 2020 Dec 1;40(4):806–820. doi: 10.1038/s41388-020-01569-5

Figure 8: YM-254890 selectively inhibits proliferation of melanoma cell lines with Gαq pathway mutations.

Figure 8:

(A) IC50 of cell lines treated for 4 days with YM-254890, grouped by mutation status shows selective inhibition of melanoma cell lines with Gαq mutations.

(B) Growth kinetics of cell lines with or without Gαq mutations, treated with YM-254890 at 1 nM or 10 nM, compared to vehicle (DMSO) over 5 days. Cells were counted at day 0, 1, 3 and 5.

(C) Cells treated with different dosages of YM for 10–14 days and stained with crystal violet.

(D) Model of Gαq signaling in uveal melanoma. CYSLTR2->Gαq->PLCβ is a linear signaling cascade that activates PKC and then branches into the MAP-kinase and FAK/YAP pathway. While the PKC->RasGRP3->MAPK signal axis is essential for UM proliferation, the FAK/YAP pathway is not. The Gαq->PLCβ->PKC-> MAP-kinase pathway is the core signaling module for targeted therapy in UM.