The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index.
Mechanisms of Hypoxic Gene Regulation of Angiogenesis Factor Cyr61 in Melanoma Cells
Open accessAbstract
Hypoxia has a profound influence on progression and metastasis of malignant tumors. In the present report, we used the oligonucleotide microarray technique to identify new hypoxia-inducible genes in malignant melanoma with a special emphasis on angiogenesis factors. A commercially available Affymetrix gene chip system was used to analyze five melanoma cell lines of different aggressiveness. A total of 160 hypoxia-inducible genes were identified, clustering in four different functional clusters. In search of putative angiogenesis and tumor progression factors within these clusters, Cyr61, a recently discovered angiogenesis factor, was identified. Cyr61 was hypoxia-inducible in low aggressive melanoma cells; however, it showed constitutive high expression in highly aggressive melanoma cells. Further analyses of transcriptional mechanisms underlying Cyr61 gene expression under hypoxia demonstrated that an AP-1 binding motif within the Cyr61 promoter plays a central role in the hypoxic regulation of Cyr61. It could be shown by use of in vitro luciferase assays, electrophoretic mobility shift assays, and immunoprecipitation that hypoxia-inducible factor-1alpha interacts with c-Jun/AP-1 and may thereby contribute to Cyr61 transcriptional regulation under hypoxia. Taken together, the presented data show that Cyr61 is a hypoxia-inducible angiogenesis factor in malignant melanoma with tumor stage-dependent expression. This may argue for a hypoxia-induced selection process during tumor progression toward melanoma cells with constitutive high Cyr61 expression.
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“Consistent with its angiogenic functions, CCN1 is highly induced under conditions of hypoxia, mediated through both hypoxia-inducible factor-1α (HIF-1α)-dependent and -independent mechanisms [25,43,44].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [25]
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RetractedLi, Z. (2024) · American Journal of Cancer Research · doi:10.62347/ckmt4065
Renaud-Gabardos, E. (2016) · theses.fr (ABES) · doi:10.70675/6d9b4309za1adz4f4aza374zddc5391a757f
Tran, A. B., & Ortiz-Hernández, G. L. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1843283
Metadata
- Authors
- Kunz, M., Moeller, S., Koczan, D., Lorenz, P., Wenger, R. H., Glocker, M. O., Thiesen, H.-J., Gross, G., & Ibrahim, S. M.
- Affiliations
- University of Rostock (DE)
- Leipzig University (DE)
- Corresponding author
- Kunz, Manfred
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 278
- Issue
- 46
- Pages
- 45651-45660
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1988530720
- Cited by
- 104
- References
- 67
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Keywords
- CYR61, hypoxia, melanoma, angiogenesis, hypoxia-responsive genes, hypoxia-inducible factor-1α, AP-1, c-Jun, transcriptional regulation, tumor progression, tumor aggressiveness, tumor stage
- MeSH terms
- Hypoxia, Humans, Luciferases, Melanoma, Plasmids, Promoter Regions, Genetic, Protein Binding, RNA, Time Factors, Transcription Factors, Blotting, Northern, Gene Expression Regulation, Neoplastic, Mutagenesis, Protein Structure, Tertiary, Immediate-Early Proteins, DNA, Complementary, Jurkat Cells, Oligonucleotide Array Sequence Analysis, Amino Acid Motifs, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit, Cysteine-Rich Protein 61
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