PMC:4307189 / 37300-38981 JSONTXT

{"project":"2_test","denotations":[{"id":"25599599-23585460-14868135","span":{"begin":623,"end":625},"obj":"23585460"},{"id":"25599599-23542173-14868136","span":{"begin":716,"end":717},"obj":"23542173"},{"id":"25599599-16618740-14868137","span":{"begin":820,"end":822},"obj":"16618740"},{"id":"25599599-7566092-14868138","span":{"begin":885,"end":887},"obj":"7566092"},{"id":"25599599-17873882-14868139","span":{"begin":998,"end":1000},"obj":"17873882"},{"id":"25599599-17114293-14868140","span":{"begin":1112,"end":1114},"obj":"17114293"},{"id":"25599599-16847353-14868141","span":{"begin":1197,"end":1199},"obj":"16847353"},{"id":"25599599-10644343-14868142","span":{"begin":1200,"end":1202},"obj":"10644343"},{"id":"25599599-11715018-14868143","span":{"begin":1555,"end":1557},"obj":"11715018"},{"id":"25599599-15735750-14868144","span":{"begin":1674,"end":1676},"obj":"15735750"},{"id":"25599599-16023600-14868145","span":{"begin":1677,"end":1679},"obj":"16023600"}],"text":"Cross-talk between EGFR/ErbB and Notch signaling\nWe investigated literature evidence regarding the putative cross-talks between EGFR/ErbB signaling and other signaling pathways. We found AKT2:MAML2 (in Reactome and KEGG), AKT2:TP53 (in Reactome), AKT2:MYC (in Reactome), KIT:MAML2 (in Reactome), KIT:TP53 (in Reactome), MDM2:MAML2 (in Reactome and WikiPathway), MDM2:TP53 (in Reactome), and TP53:MAML2 (in WikiPathway) gene-pairs as putative cross-talks between EGFR/ErbB signaling and Notch signaling pathways. Up-regulation of the Notch signaling pathway inhibits apoptosis and thus contributes to breast carcinogenesis [37]. The Notch signaling pathway cross-talks with EGFR/ErbB signaling at the mediator level [1], e.g. when activated, Notch1 contributes to cell growth and survival via Akt-activation in melanoma [38]. The Notch1 co-activator complex binds to the HES1 promoter [39] which encodes a transcription repressor that represses the expression of PTEN, a PI3K/Akt pathway inhibitor [40] contributing to tyrosine kinase inhibitor (TKI) resistance. Furthermore, Notch1 stimulates MYC transcription [41] and this stimulation can lead to the down-regulation of MYC via the Akt-pathway [42,43]. This putative gene-pair, AKT2:MYC was also found in our results as a potential drug-resistant cross-talk between the EGFR/ErbB and TGF- β receptor signaling pathways. Again, in HER2/neu-mediated resistance to DNA-damaging agents, the Akt pathway becomes activated which eventually suppresses p53 functions via enhancing MDM2-mediated ubiquitination [44]. Protein-protein interaction between MDM2 and p53 is evident as contributing to various cancer related activities [45,46]."}