Lactate stimulates CA IX expression in normoxic cancer cells

Elena Panisova; Martin Kery; Olga Sedlakova; Lucie Brisson; Michaela Debreova; Martina Sboarina; Pierre Sonveaux; Silvia Pastorekova; Eliska Svastova

doi:10.18632/oncotarget.20836

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Research Papers:

Lactate stimulates CA IX expression in normoxic cancer cells

Elena Panisova, Martin Kery, Olga Sedlakova, Lucie Brisson, Michaela Debreova, Martina Sboarina, Pierre Sonveaux, Silvia Pastorekova and Eliska Svastova _

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Oncotarget. 2017; 8:77819-77835. https://doi.org/10.18632/oncotarget.20836

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Abstract

Elena Panisova1, Martin Kery1, Olga Sedlakova1, Lucie Brisson2,3, Michaela Debreova1, Martina Sboarina2, Pierre Sonveaux2, Silvia Pastorekova1 and Eliska Svastova1

1Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia

2Unit of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium

3Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais, Tours, France

Correspondence to:

Eliska Svastova, email: [email protected]

Keywords: tumor metabolism, carbonic anhydrase IX, lactate, HIF-1, MCT1

Received: February 28, 2017 Accepted: August 08, 2017 Published: September 12, 2017

ABSTRACT

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 in vitro and in vivo. 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 CA9 gene. By inducing CA IX, lactate can facilitate the maintenance of cancer cell aggressive behavior in normoxia.

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PII: 20836

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Research Papers:

Lactate stimulates CA IX expression in normoxic cancer cells

Abstract