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Potential mechanism by which NSCLC cells with wt EGFR display resistance to erlotinib. The up-regulation of ErbB ligands (TGF-α, EREG and NRG4) activates EGFR. Activation of RAF1-MEK1-ERK and PKC/SNAI-AKT up-regulates the downstream signaling and hence confers NSCLC cells harboring wt EGFR resistance to erlotinib. The pink molecules represent that its mRNA expression is up-regulated. The orange molecules mean that it is activated.
