Fig. 3: ARF6 promotes tumor survival and accelerated disease progression.

a Apoptotic protein profile of tumor cells derived from Braf^V600E; Cdkn2a^f/f mice detected by Reverse Phase Protein Array. Two-tailed t-test, n = 3 replicates per cell line. b Western Blot for indicated proteins in murine melanoma cells derived from Braf^V600E; Cdkn2a^f/f mice. Two-tailed ratio paired t-test, n = 3 biological independent experiments. c Apoptosis detection, measured at 48 h, dox-inducible ectopic expressed ARF6^WT and ARF6^Q67L in A375 cells. One-way ANOVA with multiple comparisons, n = 4 replicates per condition. d Apoptosis detection, 4 μM QS11, measured at 48 h. Two-tailed unpaired t-test, n = 5 for A375 and n = 3 for A2058 replicates per condition. e Cell viability detection, measured at 72 h. Two-tailed unpaired t-test, n = 5 replicates per condition. f Rate of tumor growth measured from the time of initial detection in Braf^V600E; Cdkn2a^f/f; Arf6^WT mice. Two-tailed t-test with Welch’s correction, n = 24 Pten^WT, n = 14 Pten^f/f mice. g Rate of tumor growth measured from the time of initial detection in Braf^V600E; Cdkn2a^f/f; Pten^f/f mice. Two-tailed t-test with Welch’s correction, n = 14 Arf6^WT, n = 22 Arf6^f/f mice. h Survival of mice (before primary tumor reached 2 cm) after Cre injection (day 0) within 130 days, n = 14 Arf6^WT, n = 18 Arf6^f/f mice, Log-rank (Mantle-Cox) test. Solid line within data points = mean. i, Apoptotic protein profile of whole tumors from Braf^V600E; Cdkn2a^f/f; Pten^f/f mice (n = 6 mice per group) detected by Reverse Phase Protein Array, two-tailed t-test.