Cancer research (Chicago, Ill.), 2003-03, Vol.63 (5), p.1138-1143
2003
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Details
- Autor(en) / Beteiligte
- Titel
- Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1
- Ist Teil von
- Cancer research (Chicago, Ill.), 2003-03, Vol.63 (5), p.1138-1143
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. Here we demonstrate that hypoxia or HIF-1 alpha overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1 alpha. We show that HIF-1 regulates the expression of genes encoding cathepsin D; matrix metalloproteinase 2; urokinase plasminogen activator receptor (uPAR); fibronectin 1; keratins 14, 18, and 19; vimentin; transforming growth factor alpha; and autocrine motility factor, which are proteins that play established roles in the pathophysiology of invasion. Neutralizing antibodies against uPAR block tumor cell invasion induced by hypoxia or HIF-1 alpha overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1 alpha overexpression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445Titel-ID: cdi_proquest_miscellaneous_73064702
- Format
- –
- Schlagworte
- Animals, Basement Membrane - cytology, Basement Membrane - metabolism, Biological and medical sciences, Cell Hypoxia - physiology, Colonic Neoplasms - genetics, Colonic Neoplasms - metabolism, Colonic Neoplasms - pathology, Dissemination, DNA-Binding Proteins - biosynthesis, DNA-Binding Proteins - genetics, DNA-Binding Proteins - physiology, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Medical sciences, Mice, Neoplasm Invasiveness, Nuclear Proteins - biosynthesis, Nuclear Proteins - genetics, Nuclear Proteins - physiology, Receptors, Cell Surface - biosynthesis, Receptors, Cell Surface - genetics, Receptors, Cell Surface - physiology, Receptors, Urokinase Plasminogen Activator, Transcription Factors, Transfection, Tumor cell, Tumor Cells, Cultured, Tumors