國家衛生研究院 NHRI:Item 3990099045/8208
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8208


    Title: Arsenic trioxide inhibits CXCR4-mediated metastasis by interfering miR-520h/PP2A/NF-kappaB signaling in cervical cancer
    Other Titles: Arsenic trioxide inhibits CXCR4-mediated metastasis by interfering miR-520h/PP2A/NF-κB signaling in cervical cancer
    Authors: Chang, YW;Chen, MW;Chiu, CF;Hong, CC;Cheng, CC;Hsiao, M;Chen, CA;Wei, LH;Su, JL
    Contributors: National Institute of Cancer Research
    Abstract: Background Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations leading to apoptosis and differentiation in malignant cells. We and others have demonstrated that arsenic inhibits the metastatic capacity of cancer cells. Here we present additional mechanistic studies to elucidate the potential of arsenic as a promising therapeutic inhibitor of metastasis. Methods The effects of arsenic trioxide (ATO) on human cervical cancer cell lines migration and invasion were observed by transwell assays. In experimental metastasis assays, cancer cells were injected into tail veins of severe combined immunodeficient mice for modeling metastasis. The mechanisms involved in ATO regulation of CXCR4 were analyzed by immunoblot, real-time polymerase chain reaction, and luciferase reporter assays. Immunohistochemistry was utilized to identify PP2A/C and CXCR4 protein expressions in human cervical cancer tissues. Results ATO inhibited CXCR4-mediated cervical cancer cell invasion in vitro and distant metastasis in vivo. We determined that ATO modulates the pivotal nuclear factor-kappa B (NF-κB)/CXCR4 signaling pathway that contributes to cancer metastasis. Substantiating our findings, we demonstrated that ATO activates PP2A/C activity by downregulating miR-520h, which results in IKK inactivation, IκB-dephosphorylation, NF-κB inactivation, and, subsequently, a reduction in CXCR4 expression. Furthermore, PP2A/C was reduced during cervical carcinogenesis, and the loss of PP2A/C expression was closely associated with the nodal status of cervical cancer patients. Conclusions Our results indicate a functional link between ATO-mediated PP2A/C regulation, CXCR4 expression, and tumor-suppressing ability. This information will be critical in realizing the potential for synergy between ATO and other anti-cancer agents, thus providing enhanced benefit in cancer therapy.
    Date: 2014-12
    Relation: Annals of Surgical Oncology. 2014 Dec;21(4 Suppl.):687-695.
    Link to: http://dx.doi.org/10.1245/s10434-014-3812-5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1068-9265&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000345320300037
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84939884194
    Appears in Collections:[Jen-Liang Su] Periodical Articles

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