Abstract
Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1α 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-1α overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1α. 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 α; 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-1α overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1α overexpression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1138-1143 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 5 |
| State | Published - Mar 1 2003 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. / Krishnamachary, Balaji; Berg-Dixon, Shannon; Kelly, Brian; Agani, Faton; Feldser, David; Ferreira, Gloria; Iyer, Narayan; LaRusch, Jessica; Pak, Brian; Taghavi, Panthea; Semenza, Gregg L.
In: Cancer Research, Vol. 63, No. 5, 01.03.2003, p. 1138-1143.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1
AU - Krishnamachary, Balaji
AU - Berg-Dixon, Shannon
AU - Kelly, Brian
AU - Agani, Faton
AU - Feldser, David
AU - Ferreira, Gloria
AU - Iyer, Narayan
AU - LaRusch, Jessica
AU - Pak, Brian
AU - Taghavi, Panthea
AU - Semenza, Gregg L
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1α 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-1α overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1α. 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 α; 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-1α overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1α overexpression.
AB - Hypoxia-inducible factor 1 (HIF-1) transactivates genes the products of which mediate tumor angiogenesis and glycolytic metabolism. Overexpression of the HIF-1α 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-1α overexpression stimulates Matrigel invasion by HCT116 human colon carcinoma cells, whereas this process is inhibited by a small interfering RNA directed against HIF-1α. 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 α; 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-1α overexpression. These results provide a molecular basis for promotion of the invasive cancer phenotype by hypoxia and/or HIF-1α overexpression.
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UR - http://www.scopus.com/inward/citedby.url?scp=0037374289&partnerID=8YFLogxK
M3 - Article
VL - 63
SP - 1138
EP - 1143
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 5
ER -