Cited by 827Enzyme function and inhibitionCancer, Hypoxia, and MetabolismCancer and biochemical research

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Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH

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Švastová, Eliška, Hulı́ková, Alžbeta, Rafajová, Monika, Zat'ovičová, Miriam, Gibadulinová, Adriana, Casini, Angela, Cecchi, Alessandro, Scozzafava, Andrea, Supuran, Claudiu T., Pastorek, Jaromı́r, Pastoreková, Silvia·2004·FEBS Letters

DOI 10.1016/j.febslet.2004.10.043

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Abstract

Acidic extracellular pH (pHe) is a typical attribute of a tumor microenvironment, which has an impact on cancer development and treatment outcome. It was believed to result from an accumulation of lactic acid excessively produced by glycolysis. However, metabolic profiles of glycolysis-impaired tumors have revealed that CO2 is a significant source of acidity, thereby indicating a contribution of carbonic anhydrase (CA). The tumor-associated CA IX isoform is the best candidate, because its extracellular enzyme domain is highly active, expression is induced by hypoxia and correlates with poor prognosis. This study provides the first evidence for the role of CA IX in the control of pHe. We show that CA IX can acidify the pH of the culture medium in hypoxia but not in normoxia. This acidification can be perturbed by deletion of the enzyme active site and inhibited by CA IX-selective sulfonamides, which bind only to hypoxic cells containing CA IX. Our findings suggest that hypoxia regulates both expression and activity of CA IX in order to enhance the extracellular acidification, which may have important implications for tumor progression.

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Carbonic anhydrase inhibitors
Supuran, C. T., Scozzafava, A., & Casini, A. (2002) · Medicinal Research Reviews · doi:10.1002/med.10025 · Cited by 1,477
Self-citation
Hypoxia-inducible expression of tumor-associated carbonic anhydrases.
Wykoff, C. C., Beasley, N. J. P., Watson, P. H., Turner, K., Pastorek, J., Sibtain, A., Wilson, G. D., Turley, H., Talks, K., Maxwell, P. H., et al. (2000) · PubMed · Cited by 1,260
Self-citation
Causes and consequences of tumour acidity and implications for treatment
Stubbs, M., McSheehy, P. M. J., Griffiths, J. R., & Bashford, C. L. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(99)01615-9 · Cited by 781
Acidic pH enhances the invasive behavior of human melanoma cells
Mart�nez-Zaguil�n, R., Seftor, E. A., Seftor, R. E. B., Chu, Y.-W., Gillies, R. J., & Hendrix, M. J. C. (1996) · Clinical & Experimental Metastasis · doi:10.1007/bf00121214 · Cited by 507
Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo.
Fukumura, D., Xu, L., Chen, Y., Gohongi, T., Seed, B., & Jain, R. K. (2001) · PubMed · Cited by 438
Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism.
Helmlinger, G., Sckell, A., Dellian, M., Forbes, N. S., & Jain, R. K. (2002) · PubMed · Cited by 417
Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes
Ivanov, S. V., Kuzmin, I., Wei, M.-H., Pack, S., Geil, L., Johnson, B. E., Stanbridge, E. J., & Lerman, M. I. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12596 · Cited by 394
HumanMN/CA9Gene, a Novel Member of the Carbonic Anhydrase Family: Structure and Exon to Protein Domain Relationships
Opavský, R., Pastoreková, S., Zelnı́k, V., Gibadulinová, A., Stanbridge, E. J., Závada, J., Kettmann, R., & Pastorek, J. (1996) · Genomics · doi:10.1006/geno.1996.0223 · Cited by 383
Self-citation
A Transport Metabolon
Sterling, D., Reithmeier, R. A. F., & Casey, J. R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105959200 · Cited by 367
Carbonic Anhydrase: Its Inhibitors and Activators
Supuran, C. T., Scozzafava, A., & Conway, J. D. (2007) · Medical Entomology and Zoology · Cited by 349
Self-citation

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Research works printed but not linked: 7

Fukumura D., 2001, Cancer Res, 61, 6020
Helmlinger G., 2002, Clin. Cancer Res, 8, 1284
Pastorek J., 1994, Oncogene, 9, 2788
Wykoff C., 2000, Cancer Res, 60, 7075
10.1021/jm990479 · DOI
Semenza G.L., 2003, Nat. Rev, Cancer, 3, 721
Teicher B.A., 1993, Anticancer Res, 13, 1549

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Authors: Švastová, E., Hulı́ková, A., Rafajová, M., Zat'ovičová, M., Gibadulinová, A., Casini, A., Cecchi, A., Scozzafava, A., Supuran, C. T., Pastorek, J., & Pastoreková, S.
Affiliations: Slovak Academy of Sciences (SK)
University of Florence (IT)
ORCID: Švastová, Eliška
Hulı́ková, Alžbeta
Casini, Angela
Scozzafava, Andrea
Supuran, Claudiu T.
Pastorek, Jaromı́r
Pastoreková, Silvia
Venue: FEBS Letters
Publisher: Wiley
Published: 2004-10-28
Volume: 577
Issue: 3
Pages: 439-445
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/j.febslet.2004.10.043
OpenAlex: W1990331048
Cited by: 711
References: 32
Citations by year: 2026: 10 · 2025: 11 · 2024: 17 · 2023: 31 · 2022: 22 · 2021: 33 · 2020: 37 · 2019: 27 · 2018: 35 · 2017: 39 · 2016: 22 · 2015: 47 · 2014: 46 · 2013: 43 · 2012: 36
FWCI: 12.82
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
Florence Research (University of Florence) (submittedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: Bayer HealthCare
Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords: carbonic anhydrase IX, tumor hypoxia, extracellular pH, tumor acidosis, sulfonamide inhibitors, glycolysis, tumor progression
MeSH terms: Carbonic Anhydrase IX, Acidosis, Animals, Antigens, Neoplasm, Binding Sites, Carbonic Anhydrases, Cell Line, Cloning, Molecular, Culture Media, Dogs, Enzyme Inhibitors, HeLa Cells, Humans, Hydrogen-Ion Concentration, Isoenzymes, Precipitin Tests, Sulfonamides, Time Factors, Biomarkers, Tumor, Molecular Structure, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Sequence Deletion, Protein Structure, Tertiary, Biotinylation

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Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH

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