國家衛生研究院 NHRI:Item 3990099045/12086
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    题名: Lysosomal cysteine protease cathepsin S is involved in cancer cell motility by regulating store-operated Ca(2+) entry
    其它题名: Lysosomal cysteine protease cathepsin S is involved in cancer cell motility by regulating store-operated Ca2+ entry
    作者: Lin, HH;Chen, SJ;Shen, MR;Huang, YT;Hsieh, HP;Lin, SY;Lin, CC;Chang, WW;Chang, JY
    贡献者: National Institute of Cancer Research;Institute of Biotechnology and Pharmaceutical Research
    摘要: Cathepsin S (CTSS), a lysosomal cysteine protease, has been reported to be associated with extracellular matrix (ECM) degradation, thus promoting cell migration and invasion, but whether CTSS regulates other intracellular mechanisms during metastasis remains unknown. The expression of CTSS was knocked down using siRNA transfection, and enzymatic activity was inhibited by the highly-selective CTSS inhibitor RJW-58. The results of in vitro functional assays, western blot analysis, and an in vivo colonization model demonstrated that CTSS was positively related to cellular adhesive ability. Moreover, both CTSS knockdown and inhibition significantly decreased Ca(2+) influx via store-operated Ca(2+) entry (SOCE) without changing STIM1 and Orai1 expression levels, while RJW-58 dose-dependently reduced the activation of the Ca(2+)-dependent downstream effectors, NFAT1 and Rac1. The results of immunoprecipitation assays demonstrated that CTSS could bind to STIM1, which was reversed by CTSS inhibition. In addition, confocal microscopy and super-resolution imaging showed that CTSS inhibition led to STIM1 puncta accumulation in the endoplasmic reticulum and reduced the interaction between active STIM1 and EB1. In conclusion, we have demonstrated for the first time that the lysosomal cysteine protease, CTSS, plays an important role in mediating Ca(2+) homeostasis by regulating STIM1 trafficking, which leads to the suppression of cell migration and invasion.
    日期: 2019-12
    關聯: Biochimica et Biophysica Acta. Molecular Cell Research. 2019 Dec;1866(12):Article number 118517.
    Link to: http://dx.doi.org/10.1016/j.bbamcr.2019.07.012
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0167-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000498748700005
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85071494468
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