國家衛生研究院 NHRI:Item 3990099045/11053
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    题名: The role of aberrant mitochondrial phosphoenolpyruvate carboxykinase expression in pancreatic neuroendocrine tumors
    作者: Tsai, HJ;Chu, PY;Jiang, SS;Shan, YS;Hung, WC;Chen, MH;Lin, HY;Chen, YL;Chen, LT
    贡献者: National Institute of Cancer Research
    摘要: Pancreatic neuroendocrine tumor (pNET) is a rare type of pancreatic cancer. Agents targeting angiogenesis and mTOR, sunitinib and everolimus, have been shown to prolong the progression free survival by around 11 months for pNET patients. To further improve the survival of pNET, a novel treatment is needed. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), which is encoded by PCK2, was demonstrated to play a critical role in the survival program initiated upon stress in cancer metabolism. Although elevated expression of PCK2 has been found in various tumors, the role of PEPCK-M aberration in cancers is not well understood. In our study, 12 of 21 pNET patients had high expression of PEPCK-M in the tumors. Knockdown of PCK2 inhibited the proliferation of pNET cells and enhanced the sensitivity of pNET cells to mTOR inhibitors. Knockdown of PCK2 promoted glycolysis but reduced mitochondrial oxidative phosphorylation of pNET cells. Combination of mTOR inhibitors and anti-glycolysis agent synergistically inhibited the proliferation of pNET cells. Therefore targeting PEPCK-M or glycolysis combined with mTOR inhibitors is a potential therapeutic approach for the treatment of pNET.
    日期: 2018-01
    關聯: Cancer Science. 2018 Jan;109(Suppl. 1):466.
    Link to: http://dx.doi.org/10.1111/cas.13499
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000422694003154
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