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Research Paper
Regulation of the Chemokine Receptor CXCR4 and Metastasis by Hypoxia-Inducible Factor in Non Small Cell Lung Cancer Cell Lines
Yong-Lei Liu, Jin-Ming Yu, Xian-Rang Song, Xing-Wu Wang, Li-Gang Xing and Bin-Bin Gao
volume 5 | issue 10
october 2006Pages: 1320 - 1326
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Hypoxia promotes metastatic potential of tumor cells by largely unknown mechanisms. Hypoxia inducible factor (HIF) is a heterodimeric transcription factor consisting of ? and ??ARNT? subunits and plays an important role in tumor microenvironment. CXCR4 is a cell surface receptor that has been shown to mediate the metastasis of various tumors. CXCR4 induction by hypoxia is dependent on both activation of HIF and transcript stabilization. To investigate the mechanisms involved in hypoxia-induced metastasis and hypoxia-mediated chemokine receptor CXCR4 expression, we used lentiviral vector mediated RNA interfering (RNAi) to knock down expression of HIF-1? or HIF-2? in two NSCLC cell lines to investigate HIF-dependent invasion, migration and adhesion. Here we show that: (1) hypoxia is an important factor in regulating CXCR4 mediated metastasis and the cells exhibited reducing invasion, adhesion and migration in response to CXCL12 after knocking down HIF. (2) HIF-1? and HIF-2? are essential for hypoxic cellular response to cancer invasion and adhesion through up-regulation of CXCR4. HIF-1? and HIF-2? are playing important roles in tumor metastasis, which may offer for future intervention strategies. We also show that the lentivirus mediated RNAi technology is very effective on knocking down gene expression.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.