國家衛生研究院 NHRI:Item 3990099045/11545
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11545


    Title: The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance
    Authors: Han, F;Li, CF;Cai, Z;Zhang, X;Jin, G;Zhang, WN;Xu, C;Wang, CY;Morrow, J;Zhang, S;Xu, D;Wang, G;Lin, HK
    Contributors: National Institute of Cancer Research
    Abstract: PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
    Date: 2018-11-09
    Relation: Nature Communications. 2018 Nov 9;9:Article number 4728.
    Link to: http://dx.doi.org/10.1038/s41467-018-07188-9
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000449627900008
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85056277923
    Appears in Collections:[Others] Periodical Articles

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