New research offers mechanistic and clinical insights into CXC chemokine receptor 4 (CXCR4) nuclear localization in renal cell carcinoma (RCC). CXCR4 nuclear localization — which frequently occurred in RCCs, particularly metastases — was associated with poor prognosis and induced metastasis in vitro and in vivo. A mechanistic feedforward loop was identified whereby nuclear CXCR4 promoted hypoxia-inducible factor 1α (HIF-1α) accumulation, which, in turn, induced CXCR4 transcription. Clinically, CXCR4 and HIF-1α subcellular expression levels were associated with poor prognosis independently and when combined with TNM stage.
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Bao, Y. et al. A feed-forward loop between nuclear translocation of CXCR4 and HIF-1α promotes renal cell carcinoma metastasis. Oncogene https://doi.org/10.1038/s41388-018-0452-4 (2018)
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Bradley, C.A. CXCR4–HIF-1α interaction drives metastasis. Nat Rev Urol 15, 726 (2018). https://doi.org/10.1038/s41585-018-0097-7
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DOI: https://doi.org/10.1038/s41585-018-0097-7