Panisova Elena, Kery Martin, Sedlakova Olga, Brisson Lucie, Debreova Michaela, Sboarina Martina, Sonveaux Pierre, Pastorekova Silvia, Svastova Eliska
Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Unit of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL), Brussels, Belgium.
Oncotarget. 2017 Sep 12;8(44):77819-77835. doi: 10.18632/oncotarget.20836. eCollection 2017 Sep 29.
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.
除了缺氧外，其他因素和分子，如乳酸、琥珀酸和活性氧，即使在常氧条件下也能激活转录因子缺氧诱导因子-1（HIF-1）。HIF-1的主要靶基因产物之一是碳酸酐酶IX（CA IX）。CA IX在许多肿瘤中过度表达，是缺氧、侵袭性和恶性癌症的预后因素。在高细胞密度的常氧条件下也可诱导CA IX。在本研究中，我们观察到乳酸可诱导常氧癌细胞中CA IX的表达。我们进一步证明，HIF-1和特异性蛋白1（SP1）转录因子的参与对于乳酸驱动的该基因常氧诱导至关重要。通过诱导CA IX，乳酸可促进常氧条件下癌细胞侵袭行为的维持。
