國家衛生研究院 NHRI:Item 3990099045/8701
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8701


    Title: Down-regulation of ARNT promotes cancer metastasis by activating the fibronectin/integrin beta1/FAK axis
    Other Titles: Down-regulation of ARNT promotes cancer metastasis by activating the fibronectin/integrin β1/FAK axis
    Authors: Huang, CR;Lee, CT;Chang, KY;Chang, WC;Liu, YW;Lee, JC;Chen, BK
    Contributors: National Institute of Cancer Research
    Abstract: The aryl hydrocarbon receptor nuclear translocator (ARNT) is broadly involved in regulating tumorigenesis by inducing genes that are involved in tumor growth and angiogenesis. Tumorigenesis usually involves normoxic conditions. However, the role of ARNT in tumor metastasis during normoxia remains unclear. Here, we demonstrate that ARNT protein levels were decreased in late-stage human colorectal cancer using immunohistochemical analysis. Down-regulation of ARNT protein promoted cancer cell migration and invasion, which was mediated by activation of the fibronectin/integrin beta1/FAK signaling axis. In addition, the enhancement of migration and invasion in ANRT knockdown cells was blocked when ARNT was restored in the cells. In xenografts in severe combined immunodeficiency mice, tumor growth was significantly inhibited in the ARNT-knockdown condition. However, the tail-vein injection animal model revealed that the depletion of ARNT-induced metastatic lung colonies was further enhanced when ARNT expression was recovered post-injection. Interestingly, chemotherapeutic drugs inhibited ARNT expression and promoted the invasion of residual tumor cells. These results suggest that ARNT may play a positive role during tumor growth (either in early-stage tumor growth or in organ metastases), but plays a negative role in tumor migration and invasion. Therefore, the efficiency of ARNT-targeted therapy during different cancer stages should be carefully evaluated.
    Date: 2015-05
    Relation: Oncotarget. 2015 May;6(13):11530-11546.
    Link to: http://dx.doi.org/10.18632/oncotarget.3448
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000359006400066
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84929629267
    Appears in Collections:[Kwang-Yu Chang] Periodical Articles

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