FIGURE 7.

Phospho-Sam68 mediates HGF-induced Met⁺ cancer cell migration. A, MDA-MB-435 cells were transiently transfected as described above with vector, WT-, or m1-Sam68 and assayed for HGF-induced migration. B, Western blot showing transfected and endogenous Sam68 protein expression and MAPK activation. Endogenous and Myc-tagged WT- and m4-Sam68 were visualized by Western blotting using Sam68-specific antibodies. Slower running bands indicate Myc-tagged proteins. ERK1/2 activation was evaluated using phospho-specific antibodies; total ERK1/2 served as a loading control. * denotes significance (p < 0.05) relative to vehicle between indicated groups, as determined by unpaired Student's t test. C, mechanism of action of Sam68 downstream of activated Met receptors. Sam68 is the common effector of HGF-induced migration in keratinocyte and breast cancer cells. Contrary to ERK1/2- and CD44v5-dependent keratinocyte migration, breast cancer cell migration occurs independently of CD44v5 expression via an ERK1/2- or ERK5-dependent mechanism, suggesting a role for phospho-Sam68 in the regulation of splicing of multiple gene targets important for HGF-induced cell migration.