國家衛生研究院 NHRI:Item 3990099045/8067
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    题名: Utilization of liquid chromatography mass spectrometry analyses to identify LKB1-APC interaction in modulating wnt/beta-catenin pathway of lung cancer cells
    其它题名: Utilization of liquid chromatography mass spectrometry analyses to identify LKB1-APC interaction in modulating wnt/β-catenin pathway of lung cancer cells
    作者: Jian, SF;Hsiao, CC;Chen, SY;Weng, CC;Kuo, TL;Wu, DC;Hung, WC;Cheng, KH
    贡献者: National Institute of Cancer Research
    摘要: STK11/LKB1, a serine/threonine protein kinase and tumor suppressor, is a key upstream kinase of adenine monophosphate-activated protein kinase, which is a kinase involved in controlling cell polarity and maintaining cellular energy homeostasis. LKB1 is mutated in a significant number of Peutz-Jeghers syndrome (PJS) cases and sporadic cancers, and is most frequently mutated in lung adenocarcinomas; however, little is known about how LKB1 is involved in lung cancer progression. In this study, immunoprecipitation-HPLC tandem mass spectrometry (IP-LC-MS/MS) was performed to identify novel proteins interacting with LKB1 in lung cancer. Interestingly, many LKB1-interacting proteins acquired from the LC-MS/MS approach were mapped, using MetaCore pathway analysis, to the cystic fibrosis transmembrane conductance regulator activation pathway. Moreover, it was determined that LKB1 directly interacts with APC, and this LKB1-APC interaction was further confirmed by reverse immunoprecipitation assays, but GSK3 beta was dispensable for the association of LKB1 and APC. Importantly, LKB1 binds to APC to suppress the Wnt/beta-catenin signaling pathway, which is known to be involved in cell proliferation and migration. Subsequent analysis of the downstream targets of the Wnt/TCF pathway led to the identification of several Wnt-regulated genes, such as CD44, COX-2, survivin, and c-Myc, whose expression levels are downregulated by LKB1. In summary, these results demonstrate that LKB1 regulates the Wnt pathway through a direct interaction with APC to suppress the tumorigenic/metastatic potential of lung tumors. Implications: LKB1 status influences the molecular circuitry (Wnt/beta-catenin pathway), cellular biology, and may serve as a potential therapeutic node in genetically defined subsets of lung cancer.
    日期: 2014-04
    關聯: Molecular Cancer Research. 2014 Apr;12(4):622-635.
    Link to: http://dx.doi.org/10.1158/1541-7786.mcr-13-0487
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1541-7786&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000334583900014
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84925545570
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