The von Hippel-Lindau (VHL) tumor suppressor gene is inactivated in the majority of clear cell renal cell carcinomas (ccRCC), but genetic ablation of Vhl alone in mouse models is insufficient to recapitulate human tumorigenesis. One function of pVHL is to regulate the stability of the hypoxia-inducible factors (HIF), which become constitutively activated in the absence of pVHL. In established c...

Inactivation of the von-Hippel Lindau (VHL) tumor suppressor gene occurs in 90% of human clear cell renal cell carcinomas (ccRCC) and leads to the stable expression of the hypoxia-inducible factors HIF1α and HIF2α. The constitutive expression of HIF1α in a majority of VHL-deficient tumors is counterintuitive, given that HIF1α functions as a tumor suppressor in ccRCC, whereas HIF2α clearly enhan...

Increasing evidences indicate that shikonin can suppress the tumor growth. However, the mechanisms remain elusive. In the present study, we investigated the effects and mechanisms of shikonin against esophageal cancer. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in esophageal cancer tissues and cells was detected by immunohistochemistry and Western blot. ...

The cellular hypoxia-reoxygenation (H/R) model is an ideal method to study ischemia-reperfusion injury, which is associated with high mortality. The role of microRNA-30c-5p (miR-30c-5p) in the H/R epithelial cell model remains unknown. In the current study, we observed a significant reduction in apoptosis when miR-30c-5p was up-regulated. We also found decreased levels of C-caspase-3 (C-CASP3) ...

BACKGROUND Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway. METHODS We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial c...

Cells of the immune system utilize multiple mechanisms to respond to environmental signals and recent studies have demonstrated roles for two closely related proteins, the aryl hydrocarbon receptor (AHR) and hypoxia inducible factor-1α (HIF1α), in these processes. The AHR is a transcription factor that is activated by diverse ligands found in the diet and environmental pollution as well as by m...

OBJECTIVE Although immune responses drive the pathogenesis of atherosclerosis, mechanisms that control antigen-presenting cell (APC)-mediated immune activation in atherosclerosis remain elusive. We here investigated the function of hypoxia-inducible factor (HIF)-1α in APCs in atherosclerosis. APPROACH AND RESULTS We found upregulated HIF1α expression in CD11c(+) APCs within atherosclerotic pl...

The cellular response to hypoxia is characterised by a switch in the transcriptional program, mediated predominantly by the hypoxia inducible factor family of transcription factors (HIF). Regulation of HIF1 is primarily controlled by post-translational modification of the HIF1α subunit, which can alter its stability and/or activity. This study identifies an unanticipated role for the X-linked i...

BACKGROUND Exposure to cigarette smoke is a major risk factor for head and neck squamous cell carcinoma (HNSCC). We have previously established a chronic cigarette smoke extract (CSE)-treated human oral normal keratinocyte model, demonstrating an elevated frequency of mitochondrial mutations in CSE treated cells. Using this model we further characterized the mechanism by which chronic CSE treat...

The metabolism that sustains cancer cells is adapted preferentially to glycolysis, even under aerobic conditions (Warburg effect). This effect was one of the first alterations in cancer cells recognized as conferring a survival advantage. In this study, we show that gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), which was previously identified as a tumor suppressor pro...