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[摘要]：Hypoxia contributes to major aspects of cancer biology such as angiogenesis, glucose/energy metabolism, invasion and metastasis. The activation of hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a key step that promotes the transcriptional activation of target genes fundamental for these processes. In this issue of EMBO Journal, Balamurugan et al provide new insights on how hypoxia control integrates with inflammation and metastasis by describing an exciting role for the transcription factor C/EBP delta in the amplification of HIF-1 alpha signalling. The authors show that C/EBP delta promotes the transcriptional repression of the tumour suppressor F-box and WD repeat-domain containing 7 protein (FBXW7), which in turn leads to mTOR protein stabilization and increased HIF-1a levels. Although C/EBP delta can act as a tumour suppressor gene at early stages of cancer development, it appears to have a positive role in progression and metastasis, thus adding to the ranks of genes that exert opposing effects at early and late stages of tumorigenesis. |
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