Role of hypoxia inducible factor-1 in cancer stem cells (Review)

Abstract

Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo-, radio-and immuno-resistance. Understanding the mechanism of CSC self-renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial-mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor-1 (HIF-1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF-1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non-coding RNA and signaling pathways associated with HIF-1, in order to provide novel targets with HIF-1 as the core for clinical treatment, and extend the life of patients. Contents 1. Introduction 2. Structural characteristics of HIF-1 3. Role of epigenetic and post-translational modification of HIF-1 in CSCs 4. Role of HIF-1 in non-coding RNA associated with CSCs 5. Role of HIF-1 in CSC markers 6. Role of HIF-1 in tumor immunity of CSCs 7. Role of HIF-1 in metabolic reprogramming of CSCs 8. Role of HIF-1 in signaling pathways associated with CSCs 9. Potential targets for CSC therapy 10. Conclusions and perspectives

ROS and TGFβ: from pancreatic tumour growth to metastasis

“…In hypoxic conditions elevated ROS can activate hypoxia inducible factors (HIFs), heterodimers of HIF-1α, HIF-2α, or HIF-3α and HIF-β/aryl hydrocarbon receptor nuclear translocator (ARNT). While HIF-β is ubiquitously expressed in various cell types, HIF-α subunits are regulated by intracellular oxygen sensors known as prolyl hydroxylate enzymes and asparaginyl hydroxylase [50]. Interestingly, hypoxia-activated HIF proteins and TGFβactivated SMAD2/3 proteins can cooperatively regulate gene expression including PLOD2, a key enzyme for proper deposition of collagen into the ECM [51].…”

The Natural Product β-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis

“…In addition, in our study, the treatment of mice with β-escin led to a decrease in the HIF1α targeted genes LDHA, CD31, and HK2 in vivo. Because HIF1α is a notable transcription factor driving both autophagy and the associated CSC differentiation [36,37], it is plausible that the inhibition of the autophagy and CSC markers by β-escin observed here are linked to its inhibition of HIF1α. We also observed that β-escin repressed HIF1α, as well as a number of key ECM proteins in fibroblasts and mesothelial cells, which was linked with the decreased ability of OvCa cells to adhere to and invade the TME.…”

Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1

“…Hypoxia inducible factor 1-alpha (HIF1a) is a main regulator of transcriptional response to hypoxia in cancer cells. HIF1a up-regulates a number of genes that support tumor cells to adopt to the hypoxic microenvironment (5). HIF1a overexpression has been detected in solid tumors and is associated with the progression of a variety of cancers, including ovarian cancer (6), breast cancer (7), non-small cell lung cancer (8) and pancreatic cancer (9).…”