Nanoparticle-mediated activation of receptor signaling (WP2643)

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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2643 CPTAC Assay Portal]
last edited

Authors

Bart Smeets, Elisa, Egonw, Khanspers, and Laurent

Cited In

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Organism

Homo sapiens

Communities

Adverse Outcome Pathways Nanomaterials Pathways

Annotations

Pathway Ontology: signaling pathway nanomaterial response pathway

Participants

Label Type Compact Identifier
Fibronectin Protein uniprot:P02751
Amphiregulin Protein uniprot:P15514
Collagen Protein uniprot:P02452
α Protein uniprot:P56199
HRAS Protein uniprot:P01112
Apoptosis Pathway wikipathways:WP254
EGFR Protein uniprot:P00533
ROS Unknown wikidata:Q424361
NRAS Protein uniprot:P01111
KRAS Protein uniprot:P01116
RAF Protein uniprot:P04049
MAP2K1 Protein uniprot:Q02750
MAP2K2 Protein uniprot:P36507
MAPK1 Protein uniprot:P28482
JNK1 Protein uniprot:P45983
JNK2 Protein uniprot:P45984
JNK3 Protein uniprot:P53779
MAPK12 Protein uniprot:P53778
MAPK13 Protein uniprot:O15264
MAPK14 Protein uniprot:Q16539
MAPK11 Protein uniprot:Q15759
β Protein uniprot:P05556
Talin Protein uniprot:Q9Y490
Paxillin Protein uniprot:P49023
Src Protein uniprot:P12931
FAK Protein uniprot:Q05397
Sos Protein uniprot:Q07889
Grb Protein uniprot:P62993
PI3K Protein uniprot:O00329
AKT Protein uniprot:Q9Y243
Proliferation Unknown wikidata:Q189159
Inflammation Unknown wikidata:Q101991
Migration Unknown wikidata:Q189092
Angiogenesis Pathway wikipathways:WP1539
Differentiation Unknown wikidata:Q210861
ROS Unknown wikidata:Q424361

References

  1. Rauch J, Kolch W, Laurent S, Mahmoudi M. Big signals from small particles: regulation of cell signaling pathways by nanoparticles. Chem Rev. 2013 May 8;113(5):3391–406. PubMed Europe PMC Scholia