Department of Biophysics, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
International Research Agenda 3P, Medicine Laboratory, Medical University of Gdansk, Gdansk, Poland.
Eur J Cell Biol. 2024 Jun;103(2):151386. doi: 10.1016/j.ejcb.2024.151386. Epub 2024 Jan 20.
Hypoxia-inducible factors (HIFs) are transcription factors that reprogram the transcriptome for cells to survive hypoxic insults and oxidative stress. They are important during embryonic development and reprogram the cells to utilize glycolysis when the oxygen levels are extremely low. This metabolic change facilitates normal cell survival as well as cancer cell survival. The key feature in survival is the transition between acute hypoxia and chronic hypoxia, and this is regulated by the transition between HIF-1 expression and HIF-2/HIF-3 expression. This transition is observed in many human cancers and endothelial cells and referred to as the HIF Switch. Here we discuss the mechanisms involved in the HIF Switch in human endothelial and cancer cells which include mRNA and protein levels of the alpha chains of the HIFs. A major continuing effort in this field is directed towards determining the differences between normal and tumor cell utilization of this important pathway, and how this could lead to potential therapeutic approaches.
缺氧诱导因子（HIFs）是转录因子，可使细胞的转录组重新编程以在缺氧损伤和氧化应激下存活。它们在胚胎发育过程中很重要，可在氧气水平极低时将细胞重新编程为利用糖酵解。这种代谢变化有助于正常细胞和癌细胞的存活。存活的关键特征是急性缺氧和慢性缺氧之间的转变，这是由 HIF-1 表达和 HIF-2/HIF-3 表达之间的转变调节的。这种转变在许多人类癌症和内皮细胞中都观察到，被称为 HIF 开关。在这里，我们讨论了人类内皮细胞和癌细胞中 HIF 开关所涉及的机制，包括 HIFs 的α链的 mRNA 和蛋白质水平。该领域的一个主要持续努力是确定正常细胞和肿瘤细胞对这条重要途径的利用差异，以及这如何导致潜在的治疗方法。
