國家衛生研究院 NHRI:Item 3990099045/9633
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    Title: Decrease of ARNT promotes cancer metastasis by activating the fibronectin/integrin beta 1/FAK axis
    Other Titles: Decrease of ARNT promotes cancer metastasis by activating the fibronectin/integrin β 1/FAK axis
    Authors: Huang, CR;Lee, CT;Chang, KY;Chang, WC;Chen, BK
    Contributors: National Institute of Cancer Research
    Abstract: The aryl hydrocarbon receptor nuclear translocator (ARNT) is widely involved in regulating the tumorigenesis process 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 demonstrated that ARNT protein levels were decreased in late stage human colorectal cancer using an immunohistochemical analysis. Stably silence of the ARNT protein promoted cancer cell migration and invasion, which was mediated by the activation of the fibronectin/integrin β1/FAK signaling axis. In addition, ARNT knockdown-induced migration and invasion was inhibited when ARNT was restored in cells. In a xenograft analysis of severe combined immunodeficiency mice, ARNT-knockdown inhibited tumor growth. However, when ARNT expression recovered, the tumor growth of ARNT-knockdown-induced metastatic lung colonies was significantly enhanced. Interestingly, chemotherapeutic drugs inhibited ARNT expression and promoted invasion of residual tumor cells. These results suggested that ARNT may play a positive role during tumor growth (either in early stage tumor growth or in metastatic organs), but plays a negative role in tumor migration and invasion. Therefore, the efficiency of ARNT-targeted therapy in different cancer stages should be carefully evaluated.
    Date: 2015-08
    Relation: Cancer Research. 2015 Aug;75:Abstract number 523.
    Link to: http://dx.doi.org/10.1158/1538-7445.am2015-523
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000371578500499
    Appears in Collections:[Kwang-Yu Chang] Conference Papers/Meeting Abstract

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