Figure 4.

ECM proteins and integrins regulate EGFR signaling pathways in lung cancer. The crosstalk between EGFR and integrins includes many signaling pathways: (A) ligand-independent pathway, where integrins can biochemically bind to EGFR leading to its activation. EGFR can interact with integrins via forming a multimeric complex (Src, FAK, and the adaptor protein p130Cas), leading to cell survival and proliferation, (B) ligand-dependent pathway, where integrin clustering enhances EGFR signaling cascades upon EGFR ligand binding, resulting in enhancing Akt, ERK, and Ras signaling pathways, and (C) integrin trafficking controls the membrane expression of EGFR. Blue arrows for stimulation; dashed red arrows for cellular effect, and red “T” sign for inhibition.