• membrane trafficking
• metastasis

• MARVEL Domain-Containing Proteins/metabolism
• MARVEL Domain-Containing Proteins/genetics
• Animals
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/genetics
• Humans
• Liver Neoplasms/secondary
• Liver Neoplasms/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Mice
• Cell Line, Tumor
• Glycolysis
• Glucose Transporter Type 1/metabolism
• Glucose Transporter Type 1/genetics
• Gene Expression Regulation, Neoplastic
• Glucose/metabolism
• Myelin Proteins

• P50 CA210964 NCI NIH HHS
• R01 CA160069 NCI NIH HHS
• R01CA160069 Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)

• Glucose
• MCF-7
• gene expression
• glycolysis
• hypoxia
• normoxia

• Glucose transporter-1 (GLUT-1)
• metastasis
• neoadjuvant chemoradiation (CRT)
• rectal cancer (RC)
• survival

• ATP
• Colitis-associated cancer
• Colorectal cancer
• Inflammatory bowel disease
• P2X7 receptor

• Humans
• Adenosine Triphosphate
• Biomarkers
• Carcinogenesis
• Colorectal Neoplasms/metabolism
• Receptors, Purinergic P2X7/genetics
• Receptors, Purinergic P2X7/metabolism
• Signal Transduction

• NAFLD
• hepatocellular carcinoma (HCC)
• immunometabolism
• obesity
• stress pathways

The primary metabolic substrate for cells is glucose, which acts as both a source of energy and a substrate in several processes. However, being lipophilic, the cell membrane is impermeable to glucose and specific carrier proteins are needed to allow transport. In contrast to normal cells, cancer cells are more likely to generate energy by glycolysis; as this process generates fewer molecules of adenosine triphosphate (ATP) than complete oxidative breakdown, more glucose molecules are needed. The increased demand for glucose in cancer cells is satisfied by overexpression of a number of glucose transporters, and decreased levels of others. As specific correlations have been observed between the occurrence of cancer and the expression of glucose carrier proteins, the presence of changes in expression of glucose transporters may be treated as a marker of diagnosis and/or prognosis for cancer patients.

• CDX2
• CMS
• GLUT-1
• MUC2
• PD-L1
• colon cancer
• e-cadherin
• prognostic biomarker

• 17-20, RefBioII European Union Regional Development Fund (Trans-Pyrenean cooperation network program 2016-2018, INTERREG-POCTEFA)

The aim of the present study is to analyze the role of GLUT-1 in detection of early alterations occurring in oral leukoplakia. This study was to evaluate the expression of GLUT-1 in normal oral epithelium, the expression of GLUT-1 levels in the tissue samples of oral leukoplakia and to statistically compare the expression of GLUT-1 in normal epithelium and oral leukoplakia.

The study sample comprised formalin-fixed and paraffin-embedded tissue specimens from 23 cases of histopathologically diagnosed oral leukoplakia and formalin-fixed paraffin-embedded tissue specimens from 10 cases of normal oral mucosa. Sections were mounted on glass slide coated with Aminopropyltriethoxysilane (APES; Sigma chemical co., USA) and processed for subsequent immunohistochemical study to demonstrate GLUT-1.

GLUT-1 expression in normal oral mucosa revealed weak positivity in all 10 cases (100%). The oral leukoplakia cases showed immunopositivity in all 23 cases (100%) of which 10 cases (39.14%) demonstrated focal positivity and 13 cases (60.86%) of diffuse positivity. The results were compared statistically using ANOVA test was significant at P = 0.002.

The present study shows expression of GLUT-1 in leukoplakia may be used as a reliable marker to identify the high risk group for malignant transformation.

• GLUT-1
• leukoplakia
• malignant
• precancer

Glioblastomas are highly aggressive brain tumors with a particularly poor prognosis. Glucose transporter-1 (GLUT1/SLC2A1), a uniporter that is expressed by various carcinomas and may be involved in malignant neoplasm glycometabolism, may also be related to prognosis in glioblastomas. GLUT1 is essential to central nervous system glycometabolism. To clarify the exact role of GLUT1 in glioblastoma, we assessed the expression and localization of GLUT1 in patient samples by immunohistochemistry and in situ RNA hybridization. This revealed that GLUT1 was mainly expressed on perivascular and pseudopalisaded tumor cell membranes. All samples expressed GLUT1 to some degree, with 30.8% showing stronger staining. On the basis of these data, samples were divided into high and low expression groups, although SLC2A1 mRNA expression was also higher in the high GLUT1 expression group. Kaplan-Meier survival curves revealed that high GLUT1 expression associated with lower overall survival (log-rank test, p = 0.001) and worse patient prognoses (p = 0.001). Finally, MIB-1 staining was stronger in high GLUT1 expression samples (p = 0.0004), suggesting a link with proliferation. We therefore hypothesize that GLUT1 expression in glioblastomas may enhance glycolysis, affecting patient prognosis. Examination of GLUT1 in patients with glioblastomas may provide a new prognostic tool to improve outcome.

• Angiogenesis
• Glioblastomas
• Glucose transporter (GLUT)
• Warburg effect

• GLUT-1
• P2X7R
• TILs
• colorectal cancer
• prognosis

An important hallmark in cancer cells is the increase in glucose uptake. GLUT1 is an important target in cancer treatment because cancer cells upregulate GLUT1, a membrane protein that facilitates the basal uptake of glucose in most cell types, to ensure the flux of sugar into metabolic pathways. The dysregulation of GLUT1 is associated with numerous disorders, including cancer and metabolic diseases. There are natural products emerging as a source for inhibitors of glucose uptake, and resveratrol is a molecule of natural origin with many properties that acts as antioxidant and antiproliferative in malignant cells. In the present review, we discuss how GLUT1 is involved in the general scheme of cancer cell metabolism, the mechanism of glucose transport, and the importance of GLUT1 structure to understand the inhibition process. Then, we review the current state-of-the-art of resveratrol and other natural products as GLUT1 inhibitors, focusing on those directed at treating different types of cancer. Targeting GLUT1 activity is a promising strategy for the development of drugs aimed at treating neoplastic growth.

• GLUT1
• cancer metabolism
• cancer therapy
• glucose uptake inhibition
• resveratrol

• Animals
• Glucose/metabolism
• Glucose Transporter Type 1/metabolism
• Humans
• Neoplasms/metabolism
• Resveratrol/pharmacology

• disseminated tumor cell
• dormancy
• hypoxia
• hypoxia probes
• hypoxia sensor

• Animals
• Humans
• Hypoxia/metabolism
• Neoplasm Metastasis/pathology
• Neoplasms/metabolism
• Neoplasms/pathology

• P01 CA100324 NCI NIH HHS
• R01 CA218024 NCI NIH HHS
• R01 CA216248 NCI NIH HHS
• R01 CA109182 NCI NIH HHS
• R01 CA150344 NCI NIH HHS
• P30 CA196521 NCI NIH HHS

To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC).

Immunohistochemical staining of pathological samples for GPC3 and glucose transporter 1 (GLUT1), and whole-body ¹⁸F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUV_max) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify ¹⁸F-FDG uptake. In vitro¹⁸F-FDG uptake assay of GPC3-expressing HepG2 and non-GPC3-expressing RH7777 cells was used to examine the effect of GPC3 in cellular glucose metabolism. The relationships between GPC3 expression and ¹⁸F-FDG uptake, GLUT1 expression, tumour differentiation, and other clinical indicators were analysed using Spearman rank correlation, univariate and multiple logistic regression analyses.

Positive GPC3 expression was observed in 67.3% of HCC patients, including 75.0% of those with well or moderately differentiated HCC and 36.4% of those with poorly differentiated HCC. There was an inverse relationship between GPC3 expression and SUV_max (Spearman correlation coefficient = -0.281, P = 0.038) and a positive relationship between GLUT1 expression and SUV_max (Spearman correlation coefficient = 0.681, P < 0.001) in patients with HCC. Univariate analysis showed that two glucose metabolic parameters (SUV_max and T/NT ratio), tumour differentiation, lymph node metastasis, and TNM stage were all significantly associated with GPC3 expression (P < 0.05), whereas GLUT1 expression, sex, age, tumour size, intrahepatic lesion number, and distant metastasis showed no statistical association (P > 0.05). Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with HCC (P < 0.05). In vitro assay revealed that the uptake of ¹⁸F-FDG in GPC3-expressing HepG2 cells was significantly lower than that of non-GPC3-expressing RH7777 cells (t = -20.352, P < 0.001).

The present study demonstrated that GPC3 expression is inversely associated with glucose metabolism, suggesting that GPC3 may play a role in regulating glucose metabolism in HCC.

• Hepatocellular carcinoma
• Glypican-3
• ¹⁸F-FDG
• Maximum standard uptake value
• T/NT ratio
• Glucose metabolism
• Glucose transporter 1

• Adult
• Age Factors
• Aged
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Female
• Fluorodeoxyglucose F18/administration & dosage
• Glucose/metabolism
• Glypicans/metabolism
• Hep G2 Cells
• Humans
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Positron Emission Tomography Computed Tomography/methods
• Radiopharmaceuticals/administration & dosage
• Retrospective Studies
• Sex Factors
• Young Adult

Glucose transporter-1 (GLUT-1) exhibits altered expression in colorectal cancer (CRC). The aim of this study was to explore the association between GLUT-1 and survival conditions, as well as clinical features in CRC by meta-analysis.

Relevant studies were searched through predefined strategies, hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) were used as effective measures.

A total of 14 studies with 2,077 patients were included in this meta-analysis. The results showed that GLUT-1 was not significantly associated with overall survival (OS) (HR=1.28, 95% CI=0.86–1.91, p=0.22) or disease-free survival (DFS) (HR=1.71, 95% CI=0.78–3.72, p=0.179). However, subgroup analysis indicated that GLUT-1 was a significant biomarker for poor DFS in rectal cancer (HR=2.47, 95% CI=1.21–5.05, p=0.013). GLUT-1 expression was also found to be significantly correlated with the presence of lymph node metastasis (n=8, OR=2.14, 95% CI=1.66–2.75, p<0.001), T stage (n=6, OR=1.73, 95% CI=1.17–2.58, p=0.007), higher Dukes stage (n=5, OR=2.92, 95% CI=2.16–3.95, p<0.001), female sex (n=4, OR=2.92, 95% CI=2.16–3.95, p<0.001), and presence of liver metastasis (n=3, OR=1.82, 95% CI=1.06–3.12, p=0.03).

In conclusion, this meta-analysis showed that GLUT-1 was associated with poor DFS in rectal cancer (RC). Furthermore, GLUT-1 was also an indicator of aggressive clinical features in CRC.

• GLUT-1
• biomarker
• colorectal cancer
• meta-analysis
• survival

Glucose transporter 1 (GLUT1), the uniporter protein encoded by the SLC2A1 gene, is a key rate-limiting factor in the transport of glucose in cancer cells, and frequently expressed in a significant proportion of human cancers. Numerous studies have reported paradoxical evidence of the relationship between GLUT1 expression and prognosis in solid human tumors. To address this discrepancy, we conducted a thorough search of Pubmed and Web of Science for studies evaluating the expression of GLUT1 and overall survival (OS) and disease-free survival (DFS) in patients with solid cancer from 1993 to April 2016. Data from published researches were extracted and computed into odds ratio (OR). A total of 26 studies including 2948 patients met our search criteria and were evaluated. Overexpression of GLUT1 was found to significantly correlate with poor 3-year OS (OR: 2.86; 95% CI, 1.90–4.32, P < 0.00001) and 5-year OS (OR: 2.52; 95% CI, 1.75–3.61, P < 0.00001) of solid tumors. Similar results were observed when analysis of DFS was performed. Subgroup analysis revealed that elevated GLUT1 expression was associated with worse prognosis of oral squamous cell carcinoma and breast cancer. Taken together, overexpression of GLUT1 is correlated with poor survival in most solid tumors, suggesting that the expression status of GLUT1 is a vital prognostic indicator and promising therapeutic target in solid tumors.

• GLUT1
• disease-free survival
• overall survival
• prognosis
• solid tumors

Glucose transporter-1 (GLUT-1) as the major glucose transporter present in human cells is found overexpressed in a proportion of human malignancies. This meta-analysis is attempted to assess the prognostic significance of GLUT-1 for survival in various cancers.

We conducted an electronic search using the databases PubMed, Embase and Web of Science, from inception to Oct 20th, 2016. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Fourty-one studies with a total of 4794 patients were included. High GLUT-1 expression was significantly associated with poorer prognosis [overall survival: HR = 1.833 (95% CI: 1.597–2.069, P < 0.0001); disease-free survival: HR = 1.838 (95% CI: 1.264–2.673, P < 0.0001); progression-free survival: HR = 2.451 (95% CI: 1.668–3.233, P < 0.0001); disease specific survival: HR = 1.96 (95% CI: 1.05–2.871, P < 0.0001)].

High GLUT-1 expression may be an independent prognostic marker to predict poor survival in various types of cancers. Further clinical trials with high quality need to be conducted to confirm our conclusion.

• GLUT-1
• Glucose transporter-1
• cancer
• meta-analysis
• prognosis

• clinical pathological
• factors
• glucose transporter protein-1
• osteosarcoma
• overexpression
• prognosis
• survival

OBJECTIVE: The purpose of this article is to analyze the expression of Glut-1 and HK-II, the association between their expression and ¹⁸F-FDG accumulation in pancreatic cancer. METHODS: Fifty patients with histologically proven pancreatic cancer were included in this preliminary study, all of whom received ¹⁸F-FDG PET/CT performance before surgery. Immunohistochemical staining of tumor tissue and adjacent normal tissue was performed for Glut-1 and HK-II. By combining proportions and intensity of immunochemical staining, we obtained the modified immunohistological scores for Glut-1 and HK-II respectively. The relationship between expression of Glut-1, HK-II and series of parameters was analyzed, i.e. clinicopathological characteristics, prognosis of patients and SUV_max of PET-CT. RESULTS: Compared with normal tissue, the Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased (P < .001). There was no correlation between expression of Glut-1, HK-II and age, gender, tumor size, tumor location, tumor histological type, tumor differentiation, the nerve infiltration, vascular invasion, local infiltration, lymph node metastasis or tumor staging in pancreatic cancer (P > .05). During the follow-up period, the survival curves of low Glut-1 group and high Glut-1 group were statistically different (P = .049). Multivariate analysis (Cox regression) revealed that Glut-1 expression was not associated with mortality (P > .05). No statistical difference was found in the survival curves of negative HK-II group and positive HK-II group (P = .545). There was no correlation between ¹⁸F-FDG uptake and expression of Glut-1 and HK-II(P > .05). CONCLUSION: The Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased. There was no correlation between expression of Glut-1, HK-II and clinicopathological characteristics, prognosis and ¹⁸F-FDG uptake.

• biomolecular markers
• glucose transporter
• ion channels
• potassium channels
• prognostic markers

Aryl hydrocarbon receptor nuclear translocator (ARNT) 2 is a transcriptional factor related to adaptive responses against cellular stress from a xenobiotic substance. Recent evidence indicates ARNT is involved in carcinogenesis and cancer progression; however, little is known about the relevance of ARNT2 in the behavior of oral squamous cell carcinoma (OSCC). In the current study, we evaluated the ARNT2 mRNA and protein expression levels in OSCC in vitro and in vivo and the clinical relationship between ARNT2 expression levels in primary OSCCs and their clinicopathologic status by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry. Using ARNT2 overexpression models, we performed functional analyses to investigate the critical roles of ARNT2 in OSCC. ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts. In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size. Since von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase, a negative regulator of hypoxia-inducible factor (HIF1)-α, is a downstream molecule of ARNT2, we speculated that HIF1-α and its downstream molecules would have key functions in cellular growth. Consistent with our hypothesis, overexpressed ARNT2 cells showed down-regulation of HIF1-α, which causes hypofunctioning of glucose transporter 1, leading to decreased cellular growth. Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs. Therefore, ARNT2 may be a potential therapeutic target against progression of OSCCs.

• ARNT2
• GLUT-1.
• HIF1-α
• VHL
• cellular proliferation
• oral squamous cell carcinoma

• Angiogenesis
• HIF
• Hypoxia
• Necrosis
• Tumor-associated inflammation

• Animals
• Cell Hypoxia/physiology
• Colorectal Neoplasms/blood supply
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Humans
• Necrosis

• GLUT1
• JNK
• glycolysis
• melanoma
• metastasis

• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Dose-Response Relationship, Drug
• Female
• Gene Expression Regulation, Neoplastic
• Glucose Transporter Type 1/antagonists & inhibitors
• Glucose Transporter Type 1/genetics
• Glucose Transporter Type 1/metabolism
• Humans
• Hydroxybenzoates/pharmacology
• Immunohistochemistry
• JNK Mitogen-Activated Protein Kinases/metabolism
• Kaplan-Meier Estimate
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/secondary
• Male
• Matrix Metalloproteinase 2/metabolism
• Melanoma/drug therapy
• Melanoma/genetics
• Melanoma/metabolism
• Melanoma/mortality
• Melanoma/secondary
• Melanoma, Experimental/drug therapy
• Melanoma, Experimental/genetics
• Melanoma, Experimental/metabolism
• Melanoma, Experimental/secondary
• Middle Aged
• RNA Interference
• Signal Transduction
• Skin Neoplasms/drug therapy
• Skin Neoplasms/genetics
• Skin Neoplasms/metabolism
• Skin Neoplasms/mortality
• Skin Neoplasms/pathology
• Time Factors
• Tissue Array Analysis
• Transfection

• [18F]-fluoro-2-deoxyglucose positron emission tomography
• glucose transporter 1
• hypoxia-inducible factor 1α
• non-small cell lung cancer

• Leprosy
• multibacillary
• orofacial lesions
• paucibacillary

Glut-1 is a glucose transporter protein, the expression of which is upregulated in malignant cells which show increased glucose uptake. Alterations in expression of Glut-1 have been reported in several pre-malignant and malignant lesions. The objectives of the present study were to compare the expression of Glut-1 in normal persons and in patients with oral squamous cell carcinoma (OSCC), to correlate the expression of Glut-1 with respect to clinical staging of OSCC and to evaluate the expression of Glut-1 with respect to different histopathological grades of OSCC.

Thirty cases of OSCC were staged clinically and graded histopathologically. Immunohistochemical method was used to detect the expression of Glut-1 in OSCC and the same was compared with the normal subjects. The scores were compared using the chi-square test.

Glut-1 expression was detected in all grades of OSCC. A significant correlation with a P value of 0.00004 was found in immunostaining between normal and OSCC. The expression of Glut-1 was significant when compared with different clinical stages with significant P value of 0.0004 and in different histopathological grades of OSCC with a P value of 0.00001.

Higher immunohistochemical staining scores were obtained with increased clinical staging and histopathological grades of OSCC. High expression of Glut-1 may be related to poor prognosis in OSCC.

• GLUT-1
• oral squamous cell carcinoma
• prognostic marker

Metabolic reprogramming and altered energetics have become an emerging hallmark of cancer and an active area of basic, translational, and clinical cancer research in the recent decade. Development of effective anticancer therapeutics may depend on improved understanding of the altered cancer metabolism compared to that of normal cells. Changes in glucose transport and glycolysis, which are drastically upregulated in most cancers and termed the Warburg effect, are one of major focuses of this new research area. By taking advantage of the new knowledge and understanding of cancer’s mechanisms, numerous therapeutic agents have been developed to target proteins and enzymes involved in glucose transport and metabolism, with promising results in cancer cells, animal tumor models and even clinical trials. It has also been hypothesized that targeting a pathway or a process, such as glucose transport or glucose metabolism, rather than a specific protein or enzyme in a signaling pathway may be more effective. This is based on the observation that cancer somehow can always bypass the inhibition of a target drug by switching to a redundant or compensatory pathway. In addition, cancer cells have higher dependence on glucose. This review will provide background information on glucose transport and metabolism in cancer, and summarize new therapeutic developments in basic and translational research in these areas, with a focus on glucose transporter inhibitors and glycolysis inhibitors. The daunting challenges facing both basic and clinical researchers of the field are also presented and discussed.

• Cancer metabolism
• Warburg effect
• Glycolytic enzymes
• Glucose transporters
• Translational research

Membrane transporters enable efficient cellular metabolism, aid in nutrient sensing, and have been associated with various diseases, such as obesity and cancer. Genome-scale metabolic network reconstructions capture genomic, physiological, and biochemical knowledge of a target organism, along with a detailed representation of the cellular metabolite transport mechanisms. Since the first reconstruction of human metabolism, Recon 1, published in 2007, progress has been made in the field of metabolite transport. Recently, we published an updated reconstruction, Recon 2, which significantly improved the metabolic coverage and functionality. Human metabolic reconstructions have been used to investigate the role of metabolism in disease and to predict biomarkers and drug targets. Given the importance of cellular transport systems in understanding human metabolism in health and disease, we analyzed the coverage of transport systems for various metabolite classes in Recon 2. We will review the current knowledge on transporters (i.e., their preferred substrates, transport mechanisms, metabolic relevance, and disease association for each metabolite class). We will assess missing coverage and propose modifications and additions through a transport module that is functional when combined with Recon 2. This information will be valuable for further refinements. These data will also provide starting points for further experiments by highlighting areas of incomplete knowledge. This review represents the first comprehensive overview of the transporters involved in central metabolism and their transport mechanisms, thus serving as a compendium of metabolite transporters specific for human metabolic reconstructions.

• cancer
• constraint-based modeling
• human metabolism
• inborn errors of metabolism
• metabolic networks and pathways
• transport mechanisms

• glucose transporter-1
• gold nanorods
• immunoassay
• optical coherence tomography
• protein biomarkers
• surface plasmon resonance

• R21 EY020940 NEI NIH HHS

• PARP inhibitor
• androgen
• cancer
• carbogen
• hypoxia
• prostate
• radiotherapy

• Cardiovascular Diseases/prevention & control
• Diabetes Mellitus, Type 2/chemically induced
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
• Middle Aged
• Randomized Controlled Trials as Topic