Extended Data Fig. 7: Cabozantinib modulates multiple cellular constituents of plexiform neurofibroma by abrogating AXL signaling.

a, Primary Nf1-/- Schwann cells were stimulated with GAS6 (200 ng/mL) in the presence or absence of cabozantinib (100 nM). Proliferation was assessed by manual cell counting after 48 hours (n = 3 replicates per condition). **Adjusted P-value = 0.0091 unstimulated vs GAS6, **Adjusted P-value =0.0053 GAS6 vs GAS6 + cabozantinib (one-way ANOVA with Sidak’s multiple comparisons test). Data are presented as mean ± SEM. b, pAXL was detected by western blot following stimulation with GAS6 (250 ng/mL) in the presence or absence of cabozantinib (2500 nM). GAPDH is shown as a loading control. The experiment was conducted two times independently with similar results. c, Murine embryonic fibroblasts were stimulated with GAS6 (200 ng/mL) in the presence or absence of cabozantinib (2000 nM). Proliferation was assessed by manual cell counting after 48 hours (n = 6 replicates per condition). **Adjusted P-value = 0.0032 unstimulated vs cabozantinib only, ****Adjusted P-value <0.0001 unstimulated vs GAS6 only, ****Adjusted P-value <0.0001 GAS6 vs GAS6 + cabozantinib (one-way ANOVA with Sidak’s multiple comparisons test). Data are presented as mean ± SEM. d, pAXL was detected by western blot in primary murine embryonic fibroblasts following stimulation with GAS6 (250 ng/mL) from 0 to 30 minutes in the presence or absence of cabozantinib (2000 nM). GAPDH is shown as a loading control. The experiment was conducted two times independently with similar results. e, Human umbilical cord blood derived endothelial colony forming cells (ECFCs) were plated and stimulated with GAS6 (200 ng/mL) in the presence or absence of cabozantinib (100 nM). Proliferation was assessed by manual cell counting after 48 hours (n = 6 replicates per condition). ***Adjusted P-value = 0.0003 unstimulated vs GAS6, *Adjusted P-value = 0.0321 GAS6 vs GAS6 + cabozantinb, ns = not statistically significant, adjusted P-value = 0.0714 (one-way ANOVA with Sidak’s multiple comparisons test). Data are presented as mean ± SEM. pAXL was detected by western blot in ECFCs following stimulation with GAS6 (200 ng/mL) from 0 to 30 minutes in the presences or absence of cabozantinib (1000 nM). GAPDH is shown as a loading control.

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