國家衛生研究院 NHRI:Item 3990099045/7109
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    题名: Protein phosphorylation profiling using an in situ proximity ligation assay: Phosphorylation of AURKA-Elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells
    作者: Chen, TC;Liu, YW;Huang, YH;Yeh, YC;Chou, TY;Wu, YC;Wu, CC;Chen, YR;Cheng, HC;Lu, PJ;Lai, JM;Huang, CYF
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: The epidermal growth factor receptor (EGFR), which is up-regulated in lung cancer, involves the activation of mitogenic signals and triggers multiple signaling cascades. To dissect these EGFR cascades, we used 14 different phospho-EGFR antibodies to quantify protein phosphorylation using an in situ proximity ligation assay (in situ PLA). Phosphorylation at EGFR-Thr654 and -Ser1046 was EGF-dependent in the wild-type (WT) receptor but EGF-independent in a cell line carrying the EGFR-L858R mutation. Using a ProtoAarray? containing ~5000 recombinant proteins on the protein chip, we found that AURKA interacted with the EGFR-L861Q mutant. Moreover, overexpression of EGFR could form a complex with AURKA, and the inhibitors of AURKA and EGFR decreased EGFR-Thr654 and -Ser1046 phosphorylation. Immunohistochemical staining of stage I lung adenocarcinoma tissues demonstrated a positive correlation between AURKA expression and phosphorylation of EGFR at Thr654 and Ser1046 in EGFR-mutant specimens, but not in EGFR-WT specimens. The interplay between EGFR and AURKA provides an explanation for the difference in EGF dependency between EGFR-WT and EGFR-mutant cells and may provide a new therapeutic strategy for lung cancer patients carrying EGFR mutations.
    日期: 2013-03-08
    關聯: PLoS ONE. 2013 Mar 8;8(3):Article number e55657.
    Link to: http://dx.doi.org/10.1371/journal.pone.0055657
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000318679900005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84874781977
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