FIGURE 8.

Cooperative signaling between EGFR, c-Met, and integrin α6β4 promotes pancreatic cancer cell migration and invasion. Integrin α6β4 signaling enhances transcription of EGFR ligands, AREG and EREG, as well as MMP1 and EGFR (1). Translated proteins are brought to the cell surface for activation (2). Upon HGF-mediated stimulation (3), c-Met and integrin signaling cooperate to activate MMP1 (4) through the MAPK, PKC, and PI3K pathways (data not shown). MMP1 cleaves AREG and EREG proproteins (5), which in turn are released and lead to autocrine activation of EGFR (6) and result in enhanced cell migration and invasion (7).