The following materials were used: Dulbecco modified essential medium (DMEM), penicillin/streptomycin, and trypsin (Invitrogen, Carlsbad, CA); human recombinant HGF, HB-EGF, and EGF (R&D Systems, Minneapolis, MN); GM6001, a hydroxamic acid matrix metalloproteinase (MMP) inhibitor (3-(N-hydroxycarbamoyl)-2-(R)-isobutylpropionyl-l-tryptophan methylamide; Calbiochem, La Jolla, CA); antibodies against human EGFR (erbB1), erbB4, ERK 2 (p42 MAPK), phosphorylated ERK1/2 (p44/p42 MAPK), PY99, and Met (c-28; Santa Cruz Biotechnology, Santa Cruz, CA); antibodies against a major substrate of PI3K, AKT, and phospho-AKT (Cell Signaling, Beverly, MA); rabbit anti-EGFR (Tyr 845; Biosource, Camarillo, CA); c-Met antibody that recognizes the extracellular region of Met (Upstate Biotechnology, Lake Placid, NY); antibodies against erbB2 and erbB3 (Laboratory Vision; Fremont, CA); Boyden chamber (48 wells; Neuroprobe, Cabin John, MD) and polycarbonate membranes (14-μm pores; Osmonics, Inc., Livermore, CA); hydroxyurea, tyrphostin AG 1478, and all other chemicals (Sigma-Aldrich, St. Louis, MO).