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• W2078652630 abstract "Hypoxia is known to favor tumor survival and progression. Numerous studies have shown that hypoxia-inducible factor 1α (HIF-1α), an oxygen-sensitive transcription factor, is overexpressed in various types of human cancers and upregulates a battery of hypoxia-responsive genes for the growth and survival of cancer cells. Although tumor progression involves the acquisition of genetic and/or epigenetic changes that confer additional malignant traits, the underlying mechanisms of these changes remain obscure. We recently identified an alternative mechanism of HIF-1α function by which HIF-1α suppresses DNA repair by counteracting c-Myc transcriptional activity that maintains gene expression. Here, we show that this HIF-α-c-Myc pathway plays an essential role in mediating hypoxic effects on malignant progression via genetic alterations, resulting in the formation of malignant tumors with aggressive local invasion and epithelial-mesenchymal transition. We show an absolute requirement of the HIF-α-c-Myc pathway for malignant progression, whereas the canonical transcription function of HIF-1α alone is insufficient and seemingly dispensable. This study indicates that HIF-1α induction of genetic alteration is the underlying cause of tumor progression, especially by the hypoxic microenvironment." @default.
• W2078652630 created "2016-06-24" @default.
• W2078652630 creator A5062051877 @default.
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• W2078652630 date "2011-02-14" @default.
• W2078652630 modified "2023-09-25" @default.
• W2078652630 title "HIF-1α Confers Aggressive Malignant Traits on Human Tumor Cells Independent of Its Canonical Transcriptional Function" @default.
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• W2078652630 doi "https://doi.org/10.1158/0008-5472.can-10-2360" @default.
• W2078652630 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3041864" @default.
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• W2078652630 hasPublicationYear "2011" @default.
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