Hypoxia enhances CXCR4 expression by activating HIF-1 in oral squamous cell carcinoma
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- Published online on: March 1, 2009 https://doi.org/10.3892/or_00000275
- Pages: 707-712
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Abstract
Hypoxia promotes the invasive and metastatic potential of tumour cells. A recent study has shown that the activation of the chemokine receptor CXCR4 by lack of oxygen in breast cancer is HIF-1-dependent. We have previously demonstrated that CXCR4 signalling is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (OSCC). In this study, we investigated a correlation between CXCR4 and HIF-1α expression in OSCC. Immunohistochemistry showed that CXCR4 was expressed in 20 of 85 OSCC tissues, while HIF-1α was expressed in 51 of 85 samples. There was a significant correlation between the expression of CXCR4 and HIF-1α. In human OSCC cells, hypoxia markedly enhanced the expression of both HIF-1α and CXCR4. Furthermore, synthetic small interfering RNA specific for HIF-1α significantly suppressed the expression of this protein, and also attenuated the induction of CXCR4 expression under hypoxic conditions. These results indicated that HIF-1α regulated hypoxia-induced CXCR4 expression in OSCC.