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. Author manuscript; available in PMC: 2020 Apr 1.
Published in final edited form as: Cancer Res. 2019 Aug 15;79(19):5074–5087. doi: 10.1158/0008-5472.CAN-19-0244

Figure 3. Evaluation of DBL GEF downstream signaling mechanism in A375 cells.

Figure 3.

(A) DBL family members have exchange activity for members of the RHO and RAC1/CDC42 family, each having distinct signaling mechanisms. (B) The addition of the PAK inhibitor FRAX-486 (50 nM) is able to reduce vemurafenib resistance driven by MCF2 and VAV1. However, the ROCK inhibitor Fasudil did not show a consistent effect [*adjusted p < 0.001 relative to vemurafenib alone]. (C) Long-term treatment of A375 cells with a PAK inhibitor (FRAX-486) is capable of converting vemurafenib-induced cytostasis to cell killing, while long-term treatment with a ROCK inhibitor (Fasudil) (D) shows a trend of enhanced growth in vemurafenib. (E) Knockdown of RAC1 using three independent shRNAs converts vemurafenib-induced cytostasis to cell killing in long-term cultures of A375, while knockdown of either RHOA or RHOC does not impact cell growth with long-term vemurafenib treatment (F).