Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1

Balaji Krishnamachary, Shannon Berg-Dixon, Brian Kelly, Faton Agani, David Feldser, Gloria Ferreira, Narayan Iyer, Jessica LaRusch, Brian Pak, Panthea Taghavi, Gregg L Semenza

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1138-1143
Number of pages6
JournalCancer Research
Volume63
Issue number5
StatePublished - Mar 1 2003

Fingerprint

Hypoxia-Inducible Factor 1
Cell Hypoxia
Colon
Carcinoma
Urokinase Plasminogen Activator Receptors
Neoplasms
Keratin-14
Glucose-6-Phosphate Isomerase
Keratin-18
Keratin-19
Cathepsin D
Matrix Metalloproteinase 2
Transforming Growth Factors
Vimentin
Neutralizing Antibodies
Fibronectins
Small Interfering RNA
Phenotype
Gene Expression
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., ... Semenza, G. L. (2003). Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Research, 63(5), 1138-1143.

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 journalArticle

Krishnamachary, B, Berg-Dixon, S, Kelly, B, Agani, F, Feldser, D, Ferreira, G, Iyer, N, LaRusch, J, Pak, B, Taghavi, P & Semenza, GL 2003, 'Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1', Cancer Research, vol. 63, no. 5, pp. 1138-1143.
Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G et al. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Research. 2003 Mar 1;63(5):1138-1143.
Krishnamachary, Balaji ; Berg-Dixon, Shannon ; Kelly, Brian ; Agani, Faton ; Feldser, David ; Ferreira, Gloria ; Iyer, Narayan ; LaRusch, Jessica ; Pak, Brian ; Taghavi, Panthea ; Semenza, Gregg L. / Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. In: Cancer Research. 2003 ; Vol. 63, No. 5. pp. 1138-1143.
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