Tumour glycolysis: The many faces of HIF

Kelly, Catherine; Smallbone, Kieran; Brady, Michael

doi:10.1016/j.jtbi.2008.05.025

Cited by 15 publications

(18 citation statements)

References 21 publications

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“…In contrast to its normal role as a negative regulator of growth, increased levels of IGFBPs in tumors have been linked to enhanced proliferation, partly as a response to androgens and hypoxia-inducible factor-1 (HIF-1) protein. Thus, anaerobic conditions as well as IGF, can result in increased amount of HIF-1 [44]. A lack of vascular supply at the early stages of tumorigenesis in highly proliferating tumor cells results in hypoxia [44].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, anaerobic conditions as well as IGF, can result in increased amount of HIF-1 [44]. A lack of vascular supply at the early stages of tumorigenesis in highly proliferating tumor cells results in hypoxia [44]. Under hypoxic circumstances glycolysis becomes the dominant pathway for energy production in tumors and glycolytic enzymes are induced.…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis

et al. 2011

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BackgroundDNA methylation is an epigenetic mechanism associated with regulation of gene expression and it is modulated during chemical carcinogenesis. The zebrafish is increasingly employed as a human disease model; however there is a lack of information on DNA methylation in zebrafish and during fish tumorigenesis.ResultsA novel CpG island tiling array containing 44,000 probes, in combination with immunoprecipitation of methylated DNA, was used to achieve the first comprehensive methylation profiling of normal adult zebrafish liver. DNA methylation alterations were detected in zebrafish liver tumors induced by the environmental carcinogen 7, 12-dimethylbenz(a)anthracene. Genes significantly hypomethylated in tumors were associated particularly with proliferation, glycolysis, transcription, cell cycle, apoptosis, growth and metastasis. Hypermethylated genes included those associated with anti-angiogenesis and cellular adhesion. Of 49 genes that were altered in expression within tumors, and which also had appropriate CpG islands and were co-represented on the tiling array, approximately 45% showed significant changes in both gene expression and methylation.ConclusionThe functional pathways containing differentially methylated genes in zebrafish hepatocellular carcinoma have also been reported to be aberrantly methylated during tumorigenesis in humans. These findings increase the confidence in the use of zebrafish as a model for human cancer in addition to providing the first comprehensive mapping of DNA methylation in the normal adult zebrafish liver.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis

et al. 2011

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“…The issue of the relationship between FDG uptake within tumors and hypoxia had already been addressed by several authors [29,30]. However, to date, no study has successfully clarified the correlation between vascularity and glucose metabolism in primary oral SCC.…”

Section: Discussionmentioning

confidence: 99%

Increased glucose metabolism by FDG-PET correlates with reduced tumor angiogenesis in oral squamous cell carcinoma

et al. 2011

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Hypoxia is known to have been related with angiogenesis and glycolysis, and may have an influence on tumor treatment effect. Because glucose utilization is higher in malignant cells than that in normal cells, dynamic glucose metabolism of tumor has been evaluated by means of [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET). To investigate the significance of tumor vascularization in oral squamous cell carcinoma, we compared tumor angiogenesis with the FDG-PET findings. Twenty patients underwent FDG-PET. For the quantitative evaluation of FDG uptake in each tumor, the mean standardized uptake value (SUV) was calculated. Microvessel structures labeled with CD34 antigen were investigated in pretreatment biopsy specimens. Using an image analyzer, we calculated the following microvessel parameters: the ratio of the total number of microvessels (TN) to tumor area (TA), the ratio of the total microvessel perimeter (TP) to the TA, and the ratio of the tumor tissue area more than 150 μm distant from each microvessel (hypoxic ratio, %). The SUV was compared with the above parameters. Simple regression analysis revealed a statistical significance between the SUV and the TN:TA ratio (p = 0.046), as well as between the SUV and the TP:TA ratio (p = 0.0206). The SUV was found to be inversely related to the TN:TA and TP:TA ratios. Elevated glucose metabolism assessed by FDG-PET correlated with reduced vascularization. Higher glucose metabolism might therefore reflect a state of hypoxia.

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“…In zebrafish HCC, several IGF-binding proteins (IGFBPs), such as igfbp2b, were significantly hypomethylated and may have upregulated the expression of IGF-2 (Mirbahai et al, 2011). In the early stages of tumorigenesis in highly proliferating tumor cells, the lack of a vascular supply results in hypoxia (Kelly et al, 2008;Mirbahai et al, 2011). The anaerobic conditions and the presence of IGF result in increased expression of hypoxiainducible factor 1 (HIF-1) (Kelly et al, 2008).…”

Section: The Hgf/c-met Egfr and Igf Signaling Pathwaymentioning

confidence: 99%

“…In the early stages of tumorigenesis in highly proliferating tumor cells, the lack of a vascular supply results in hypoxia (Kelly et al, 2008;Mirbahai et al, 2011). The anaerobic conditions and the presence of IGF result in increased expression of hypoxiainducible factor 1 (HIF-1) (Kelly et al, 2008).…”

Section: The Hgf/c-met Egfr and Igf Signaling Pathwaymentioning

confidence: 99%

Liver development and cancer formation in zebrafish

Hsia

et al. 2011

Birth Defects Research Part C: Embryo Today: Reviews

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Liver is the largest organ in the human body, and it regulates many physiological processes. Many studies on liver development in different model organisms have demonstrated that the mechanism of hepatogenesis is conserved in vertebrates. The identification of the genes and regulatory pathways involved in liver formation provides a basis for the diagnosis of liver diseases and therapeutic interventions. Hepatocellular carcinoma is the third leading cause of mortality worldwide. In the last decade, genetic alterations, which include the gain and loss of DNA, as well as mutations and epigenomic changes, have been identified as important factors in liver cancer. Many genetic pathways are dysregulated during carcinogenesis. Here, we review the gene regulatory networks that underlie liver organogenesis and the dysregulation of these pathways in liver cancer. The genes and pathways involved in hepatogenesis and liver cancer are largely conserved between zebrafish and humans, making this an ideal model organism for the study of this disease. A better understanding of liver development may aid in the development of new diagnostic and therapeutic approaches to liver cancer.

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Tumour glycolysis: The many faces of HIF

Cited by 15 publications

References 21 publications

Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis

Comprehensive profiling of zebrafish hepatic proximal promoter CpG island methylation and its modification during chemical carcinogenesis

Increased glucose metabolism by FDG-PET correlates with reduced tumor angiogenesis in oral squamous cell carcinoma

Liver development and cancer formation in zebrafish

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