EGFR
epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)
requires dimerisation for activity and downstream signalling [Pubmed]; receptor tyrosine kinase [Pubmed]
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role in cancer | oncogene |
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differentiation and development | takes part in morphogenesis of epithelial organs including mammary glands [Pubmed] |
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types of alteration in cancer | frequently amplified, missense mutations and in frame deletions clustered within the extracellular domain result in constantly activated protein in glioblastoma [Pubmed]; frequently overexpressed in NSCLC [Pubmed]; recurrent L858R, E746delELREA, T790M, G719A, G719S, S768I [Pubmed] |
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impact of mutation on function | mutations clustered within tyrosine kinase domain increase activity and delay inactivation of EGFR in NSCLC [Pubmed]; L858R causes abnormally high activity, primarily by promoting EGFR dimerisation through suppressing the disorder in the alphaC-helix region [Pubmed]; deletions in exon 19 cause truncation of the beta3-alphaC loop and restrain alphaC in an active "in" conformation, imparting resistance to inhibitors like vemurafenib that bind the alphaC "out" conformation [Pubmed] |
angiogenesis
activation of the EGFR pathway is involved in tumour associated angiogenesis [Pubmed]
escaping programmed cell death
activation of EGFR protects against anoikis [Pubmed]; activating mutations within the tyrosine kinase domain activate anti-apoptotic pathways [Pubmed]
proliferative signalling
promotes cell proliferation [Pubmed]; miR-133a inhibits cervical cancer growth by targeting EGFR [Pubmed]
invasion and metastasis
upregulation of EGFR and c-Met is associated with epithelial mesenchymal transition in response to increased matrix rigidity in lung adenocarcinoma [Pubmed]; EGFR-L858R mutant enhances lung adenocarcinoma cell invasive ability and promotes malignant pleural effusion formation through activation of the CXCL12-CXCR4 pathway [Pubmed]; promotes metastasis by altering mitochondria dynamics in NSCLC [Pubmed]
change of cellular energetics
EGFR inhibitors reverse Warburg effect and reactivate oxidative phosphorylation of cancer cells in NSCLC [Pubmed]; stimulates mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo in NSCLC [Pubmed]; EGFR signalling enhances aerobic glycolysis in Triple-Negative Breast Cancer cells to promote tumour growth and immune escape [Pubmed]
escaping immune response to cancer
EGFR activation by exon-19 deletions and L858R mutation in NSCLC induces PD-L1 expression through p-ERK1/2/p-c-Jun, which may induce the apoptosis of T cells through the PD-L1/PD-1 axis and thus enable immune escape [Pubmed]