In severely hypoxic condition, HIF-1α-mediated induction of Pdk1 was found to regulate glucose oxidation by preventing the entry of pyruvate into the tricarboxylic cycle. Monocyte-derived macrophages, however, encounter a gradual decrease in oxygen availability during its migration process in inflammatory areas. Here we show that HIF-1α-PDK1-mediated metabolic changes occur in mild hypoxia, where mitochondrial cytochrome c oxidase activity is unimpaired, suggesting a mode of glycolytic reprogramming. In primary macrophages, PKM2, a glycolytic enzyme responsible for glycolytic ATP synthesis localizes in filopodia and lammelipodia, where ATP is rapidly consumed during actin remodelling processes. Remarkably, inhibition of glycolytic reprogramming with dichloroacetate significantly impairs macrophage migration in vitro and in vivo. Furthermore, inhibition of the macrophage HIF-1α-PDK1 axis suppresses systemic inflammation, suggesting a potential therapeutic approach for regulating inflammatory processes. Our findings thus demonstrate that adaptive responses in glucose metabolism contribute to macrophage migratory activity.

In 2008, Korea Centers for Disease Control and Prevention initiated the first nationwide survey, Korea Community Health Survey (KCHS), to provide data that could be used to plan, implement, monitor, and evaluate community health promotion and disease prevention programs. This community-based cross-sectional survey has been conducted by 253 community health centers, 35 community universities, and 1500 interviewers. The KCHS standardized questionnaire was developed jointly by the Korea Centers for Disease Control and Prevention staff, a working group of health indicators standardization subcommittee, and 16 metropolitan cities and provinces with 253 regional sites. The questionnaire covers a variety of topics related to health behaviors and prevention, which is used to assess the prevalence of personal health practices and behaviors related to the leading causes of disease, including smoking, alcohol use, drinking and driving, high blood pressure control, physical activity, weight control, quality of life (European Quality of Life-5 Dimensions, European Quality of Life-Visual Analogue Scale, Korean Instrumental Activities of Daily Living ), medical service, accident, injury, etc. The KCHS was administered by trained interviewers, and the quality control of the KCHS was improved by the introduction of a computer-assisted personal interview in 2010. The KCHS data allow a direct comparison of the differences of health issues among provinces. Furthermore, the provinces can use these data for their own cost-effective health interventions to improve health promotion and disease prevention. For users and researchers throughout the world, microdata (in the form of SAS files) and analytic guidelines can be downloaded from the KCHS website (http://KCHS.cdc.go.kr/) in Korean.

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.

Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1␣ and aryl hydrocarbon receptor nuclear translocator (ARNT), plays a key role in cell survival and angiogenesis in hypoxic tumors, and many efforts have been made to develop anticancer agents that target HIF-1␣. However, although ARNT is also required for HIF-1 activity, ARNT has been disregarded as a therapeutic target. Curcumin is a commonly used spice and coloring agent with a variety of beneficial biological effects, which include tumor inhibition. In the present study, we tested the possibility that curcumin inhibits tumor growth by targeting HIF-1. The effects of curcumin on HIF-1 activity and expression were examined in cancer cell lines and in xenografted tumors. We found that curcumin inhibits HIF-1 activity and that this in turn down-regulates genes targeted by HIF-1. Moreover, of the two HIF-1 subunits, only ARNT was found to be destabilized by curcumin in several cancer cell types, and furthermore, ARNT expression rescued HIF-1 repression by curcumin. We also found that curcumin stimulated the proteasomal degradation of ARNT via oxidation and ubiquitination processes. In mice bearing Hep3B hepatoma, curcumin retarded tumor growth and suppressed ARNT, erythropoietin, and vascular endothelial growth factor in tumors. These results suggest that the anticancer activity of curcumin is attributable to HIF-1 inactivation by ARNT degradation.