國家衛生研究院 NHRI:Item 3990099045/9766
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    题名: Extracellular PKM2 induces cancer proliferation by activating the EGFR signaling pathway
    作者: Hsu, MC;Hung, WC;Yamaguchi, H;Lim, SO;Liao, HW;Tsai, CH;Hung, MC
    贡献者: National Institute of Cancer Research
    摘要: Pyruvate kinase is a key enzyme in the glycolytic pathway that converts phosphoenolpyruvate to pyruvate, and the M2 isoform of pyruvate kinase (PKM2) is associated with cancer. PKM2 has been reported to function independently of its pyruvate kinase activity, which is crucial for cancer cell proliferation. Moreover, there is growing evidence indicating that dimeric PKM2 is released from tumor cells into the circulation of cancer patients. However, the role of secreted PKM2 in cancer is not well understood. Here, we found that the phosphorylation level of epidermal growth factor receptor (EGFR) significantly increased upon the exposure of cells to the recombinant PKM2 protein. In addition, secreted PKM2 induces EGFR phosphorylation and activates the EGFR downstream signaling in triple-negative breast cancer cells. In contrast, knocking down PKM2 decreased EGFR phosphorylation. Moreover, expression of R399E mutant PKM2, which has been reported to preferentially form a dimer, enhanced EGFR phosphorylation, cellular transformation, and cell proliferation more strongly than the wild-type PKM2. Thus, our study revealed a novel function of extracellular PKM2 in the promoting cancer cell proliferation through EGFR activation.
    日期: 2016-02
    關聯: American Journal of Cancer Research. 2016 Feb;6(3):628-638.
    Link to: http://dx.doi.org/ajcr0025660
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2156-6976&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000374950800005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84992310438
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