Nanoparticle-mediated activation of receptor signaling (Homo sapiens)

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Nanoparticle-mediated activation of receptor signaling. Several NP formulations were shown to interact with cellular receptors such as the EGFR and integrins, inducing cellular phenotypes such as proliferation, apoptosis, differentiation, and migration. In lung epithelial cells, NPs interact with both EGFR and integrins, leading to cell proliferation via activation of PI3K and AKT. NPs were shown to activate the EGFR, leading in parallel to apoptosis and proliferation, and oncogenic Ras mutations might influence these effects. Interestingly, while integrin-mediated activation of ERK was instrumental for proliferation, apoptosis was mediated via activation of JNK. In addition, NPs (PM2.5) are able to bind the EGFR to activate the MAPK signaling cascade. Activation of ERK leads to the expression and secretion of the epidermal growth factor amphiregulin, thus forming an autocrine loop, which might be instrumental for sustained inflammatory responses. Nanoparticles are depicted as red circles.