國家衛生研究院 NHRI:Item 3990099045/12108
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    题名: Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis
    其它题名: Dysregulation of cystathionine gamma-lyase promotes prostate cancer progression and metastasis
    作者: Wang, YH;Huang, JT;Chen, WL;Wang, RH;Kao, MC;Pan, YR;Chan, SH;Tsai, KW;Kung, HJ;Lin, KT;Wang, LH
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Hydrogen sulfide (H2 S), an endogenous signaling gaseous molecule, is involved in various physiological activities, including vessel relaxation, regulation of cellular bioenergetics, inflammation, and angiogenesis. By using xenograft orthotopic implantation of prostate cancer PC3 cells and subsequently comparing bone metastatic with primary tumor-derived cancer cells, we find that H2 S-producing enzyme cystathionine gamma-lyase (CTH) is upregulated in bone-metastatic PC3 cells. Clinical data further reveal that the expression of CTH is elevated in late-stage prostate cancer patients, and higher CTH expression correlates with poor survival from The Cancer Genome Atlas (TCGA) prostate cancer RNA-seq datasets. CTH promotes NF-kappaB nuclear translocation through H2 S-mediated sulfhydration on cysteine-38 of the NF-kappaB p65 subunit, resulting in increased IL-1beta expression and H2 S-induced cell invasion. Knockdown of CTH in PC3 cells results in the suppression of tumor growth and distant metastasis, while overexpression of CTH in DU145 cells promotes primary tumor growth and lymph node metastasis in the orthotopic implanted xenograft mouse model. Together, our findings provide evidence that CTH generated H2 S promotes prostate cancer progression and metastasis through IL-1beta/NF-kappaB signaling pathways.
    日期: 2019-08-29
    關聯: EMBO Reports. 2019 Aug 29:Article number e45986.
    Link to: http://dx.doi.org/10.15252/embr.201845986
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1469-221X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000484149600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85071369713
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