The protein family of glucose transport facilitators: It's not only about glucose after all

Augustin, Robert

doi:10.1002/iub.315

Cited by 321 publications

(259 citation statements)

References 151 publications

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“…S3). Although low glucose level could also induce a high level of GLUT-1, hypoxia would be the most possible cause of the increased GLUT-1 in our study due to the following reasons: GLUT-2, instead of GLUT-1, mediates glucose uptake in hepatocyte (14); therefore, a low glucose level in liver cancer cells may not trigger the overexpression of GLUT1; there is a documented strong association between hypoxia and liver tumor (15,16) that correlated the increased hypoxia with the observation of high level of the GLUT-1 in our study.…”

Section: Resultsmentioning

confidence: 76%

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

501

386

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The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotictreated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.H epatocellular carcinoma (HCC) is one of the most common cancers, the sixth most common neoplasm, and the second most deadly type of cancer worldwide (1). The traditional HCC treatment, including surgical treatment, local ablation therapy, and chemotherapy, could offer potential cure, yet patients are facing many limitations including the poor hepatic reserve. HCC is clearly a disease for which alternative therapeutic strategies must be developed. A better understanding of the interactions between cancer cells and stromal components in the tumorassociated proinflammatory microenvironment would be important for the management of this disease.The tumor microenvironment is infiltrated with various immune cells such as T cells, macrophages, neutrophils, natural killer (NK) cells, and myeloid-derived suppressor cells. Inflammation is known to play a pivotal role in tumor development by escalating tumor angiogenesis and cell growth. Once a solid tumor is formed, inflammation arises in the tumor-promoting direction. At the same time, new vasculature is needed in the tumor to provide nutrients and oxygen to support the growth of cancer cells, and this process plays a critical role in HCC, a highly vascularized tumor (2). Inflammation and angiogene...

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Section: Resultsmentioning

confidence: 76%

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Sung

Lee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

501

386

View full text Add to dashboard Cite

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“…The glucose site interacts predominantly with the C-terminal domain of hGLUT1. As in other secondary transporters, the binding site of this uniporter is specific for its natural substrates (19). By using intermediate water molecules, glucose achieves selectivity within a much larger binding site than the substrate.…”

Section: Discussionmentioning

confidence: 97%

Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides

Kapoor

Finer-Moore

Pedersen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

180

220

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Cancerous cells have an acutely increased demand for energy, leading to increased levels of human glucose transporter 1 (hGLUT1). This up-regulation suggests hGLUT1 as a target for therapeutic inhibitors addressing a multitude of cancer types. Here, we present three inhibitor-bound, inward-open structures of WT-hGLUT1 crystallized with three different inhibitors: cytochalasin B, a nine-membered bicyclic ring fused to a 14-membered macrocycle, which has been described extensively in the literature of hGLUTs, and two previously undescribed Phe amide-derived inhibitors. Despite very different chemical backbones, all three compounds bind in the central cavity of the inward-open state of hGLUT1, and all binding sites overlap the glucose-binding site. The inhibitory action of the compounds was determined for hGLUT family members, hGLUT1-4, using cell-based assays, and compared with homology models for these hGLUT members. This comparison uncovered a probable basis for the observed differences in inhibition between family members. We pinpoint regions of the hGLUT proteins that can be targeted to achieve isoform selectivity, and show that these same regions are used for inhibitors with very distinct structural backbones. The inhibitor cocomplex structures of hGLUT1 provide an important structural insight for the design of more selective inhibitors for hGLUTs and hGLUT1 in particular.X-ray structure | glucose facilitator | human MFS transporter | cytochalasin B | GLUT inhibitor

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“…Among the transporters, three genes of the Class II glucose transporters SLC2A7, SLC2A9 and SLC2A11 (Supporting Information Table 2) show coding polymorphisms with allele differences between populations. Class II glucose transporters have the ability to transport fructose [49]. Since fructose is implicated in obesity pathogenesis [8,12], differences in the allele frequencies across populations may result in different amounts of fructose influx into the metabolic pathways, which may produce differences in susceptibility to fructose-induced conditions.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate metabolic pathway genes associated with quantitative trait loci (QTL) for obesity and type 2 diabetes: Identification by data mining

Varma

Wise

Kaput

2010

Biotechnology Journal

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Increasing consumption of refined carbohydrates is now being recognized as a primary contributor to the development of nutritionally related chronic diseases such as obesity and type 2 diabetes mellitus (T2DM). A data mining approach was used to evaluate the role of carbohydrate metabolic pathway genes in the development of obesity and T2DM. Data from public databases were used to map the position of the carbohydrate metabolic pathway genes to known quantitative trait loci (QTL) for obesity and T2DM and for examining the pathway genes for the presence of sequence and structural genetic variants such as single nucleotide polymorphisms (SNPs) and copy number variants (CNS), respectively. The results demonstrated that a majority of the genes of the carbohydrate metabolic pathways are associated with QTL for obesity and many for T2DM. In addition, some key genes of the pathways also encode non-synonymous SNPs that exhibit significant differences in population frequencies. This study emphasizes the significance of the metabolic pathways genes in the development of disease phenotypes, its differential occurrence across populations and between individuals, and a strategy for interpreting an individuals' risk for disease.

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The protein family of glucose transport facilitators: It's not only about glucose after all

Cited by 321 publications

References 151 publications

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides

Carbohydrate metabolic pathway genes associated with quantitative trait loci (QTL) for obesity and type 2 diabetes: Identification by data mining

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