(a–d) NHEKs with and without GM3 modulation were starved overnight and treated for 2 minutes with or without IGF-1. Phosphorylation and expression of (a) IGF1R and (b) cofilin were examined by Western blotting. Activation of (c) Rac1 or (d) RhoA was determined by G-LISA. (e) IGF1R, Rac1, and Rho-associated protein kinase were inhibited with small molecule inhibitors (Inh) or shRNA (see Supplementary Figure S5). Cell migration was accessed by scratch assay. Scale bar (upper left image) = 100 μm. **P < 0.01, ***P < 0.001. AS, antisense DNA; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; G-LISA, small G-protein activation ELISA; Glu, glucose; h, hours; IGF-1, insulin-like growth factor-1; IGF1R, insulin-like growth factor-1 receptor; Inh, inhibitor; IR, insulin receptor; NHEK, normal human epidermal keratinocyte; NT, no treatment; Scr, scrambled; SE, sense; shRNA, short hairpin RNA; si, small interfering RNA; SNA, spherical nucleic acid; Veh, vehicle.