Lactate stimulates CA IX expression in normoxic cancer cells

Besides hypoxia, other factors and molecules such as lactate, succinate, and reactive oxygen species activate transcription factor hypoxia-inducible factor-1 (HIF-1) even in normoxia. One of the main target gene products of HIF-1 is carbonic anhydrase IX (CA IX). CA IX is overexpressed in many tumor...

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Published inOncotarget Vol. 8; no. 44; pp. 77819 - 77835
Main Authors Panisova, Elena, Kery, Martin, Sedlakova, Olga, Brisson, Lucie, Debreova, Michaela, Sboarina, Martina, Sonveaux, Pierre, Pastorekova, Silvia, Svastova, Eliska
Format Journal Article
LanguageEnglish
Published United States Impact journals 29.09.2017
Impact Journals LLC
Subjects
Cancer
Cellular Biology
Food and Nutrition
Life Sciences
Research Paper
HIF-1
carbonic anhydrase IX
lactate
tumor metabolism
MCT1
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Summary:Besides hypoxia, other factors and molecules such as lactate, succinate, and reactive oxygen species activate transcription factor hypoxia-inducible factor-1 (HIF-1) even in normoxia. One of the main target gene products of HIF-1 is carbonic anhydrase IX (CA IX). CA IX is overexpressed in many tumors and serves as prognostic factor for hypoxic, aggressive and malignant cancers. CA IX is also induced in normoxia in high cell density. In this study, we observed that lactate induces CA IX expression in normoxic cancer cells and . We further evidenced that participation of both HIF-1 and specificity protein 1 (SP1) transcription factors is crucial for lactate-driven normoxic induction of the gene. By inducing CA IX, lactate can facilitate the maintenance of cancer cell aggressive behavior in normoxia.
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PMCID: PMC5652817
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.20836