Variability in glucose transporter-1 levels and hexokinase activity in human melanoma

Wachsberger, Phyllis; Gressen, E L; Bhala, Ajay; Bobyock, Suzanne B.; Storck, Christopher; Coss, Ronald A.; Berd, David; Leeper, Dennis B.

doi:10.1097/00008390-200202000-00006

Cited by 28 publications

(26 citation statements)

References 39 publications

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“…Other laboratories have reported trends between GLUT-1 expression and some melanoma features of increased tumor aggressiveness [104, 105]. However, GLUT-1's role in melanoma progression requires further investigation using large number of specimens as other investigators have reported a decreased frequency of GLUT-1 in aggressive melanomas as compared to melanocytic nevi [106], or have reported variable effects on glucose uptake in melanomas [107-109]. …”

Section: Resultsmentioning

confidence: 99%

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Slominski

Kim

Brożyna

et al. 2014

Archives of Biochemistry and Biophysics

191

190

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To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic emzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.

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Section: Resultsmentioning

confidence: 99%

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Slominski

Kim

Brożyna

et al. 2014

Archives of Biochemistry and Biophysics

191

190

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“…glycolytic pathway (46). Upon transport into the cells, glucose and 2-DG are phosphorylated to glucose-PO4 and 2-DG-PO4 respectively by the hexokinase.…”

Section: -------------------------------------------------mentioning

confidence: 99%

Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers

Yeh

Wang²,

Chung³

et al. 2008

Oncol Rep

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Abstract. We investigated gene expressions involved in the glycolytic pathways in colorectal cancer. The study was designed to use gene ontology and its relevant bioinformatics tools to analyze the microarray data obtained from CRC tissues and their corresponding normal tissues, in order to explore the correlation between the glycolytic metabolic pathway and possible pathogenesis of this disease. The overexpression of glycolysis-related genes was observed in over 76% of CRC tissues. In addition, we stimulated the SW480 and SW620 CRC cell lines with 15 mM D-(+)-glucose and 10 mM 2-deoxy-D-glucose respectively. The results indicate that the proliferation response of both the SW480 and SW620 cell lines increased remarkably with a time-dependent effect by D-(+)-glucose administration. In contrast, the proliferation response of both the SW480 and SW620 cell lines was significantly inhibited by 2-DG administration. Likewise, further analyses of the expression of related genes triggered by the D-(+)-glucose in vivo show that the activation process of these eight genes -GLUT1, HK1, GPI, GAPD, PGK1, PGK2, ENO2, PKM2 -prominently increased with a timedependent effect. In conclusion, this study demonstrates that the glycolytic pathway and glycolysis-related genes may play an important role in the tumorigenesis of CRC, but their molecular mechanisms need further investigation to verify this.

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“…Glut-1 is the glucose uptake receptor active in tumor tissue. Uptake of glucose during hyperglycemia causes a transient lactic acidosis, via stimulation of glycolysis, that can potentiate hyperthermia induced acidification and cell death in human tumors [Thistlethwaite et al, 1987;Leeper et al, 1998;Wachsberger et al, 2002]. Hypoxia is a major contributor to tumor acidity and also activates the hypoxia-inducible factor, HIF-1a.…”

Section: Other Factors Affecting Regulation Ofmentioning

confidence: 99%

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

Wahl

Kenan

Gonzalez-Gronow

et al. 2005

J of Cellular Biochemistry

114

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Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as ''angiogenesis'' [Folkman (1971) N Engl J Med 285:1182-1186. These new vessels arise from local capillaries, arteries, and veins in response to the release of soluble growth factors from the tumor mass, enabling these tumors to grow beyond the diffusion-limited size of approximately 2 mm diameter. Angiostatin, a naturally occurring inhibitor of angiogenesis, was discovered based on its ability to block tumor growth in vivo by inhibiting the formation of new tumor blood vessels [O'Reilly et al. (1994a) Cold Spring Harb Symp Quant Biol 59:471-482]. Angiostatin is a proteolytically derived internal fragment of plasminogen and may contain various members of the five plasminogen ''kringle'' domains, depending on the exact sites of proteolysis. Different forms of angiostatin have measurably different activities, suggesting that much remains to be elucidated about angiostatin biology. A number of groups have sought to identify the native cell surface binding site(s) for angiostatin, resulting in at least five different binding sites proposed for angiostatin on the surface of endothelial cells (EC). This review will consider the data supporting all of the various reported angiostatin binding sites and will focus particular attention on the angiostatin binding protein identified by our group: F 1 F O ATP synthase. There have been several developments in the quest to elucidate the mechanism of action of angiostatin and the regulation of its receptor. The purpose of this review is to describe the highlights of research on the mechanism of action of angiostatin, its' interaction with ATP synthase on the EC surface, modulators of its activity, and issues that should be explored in future research related to angiostatin and other anti-angiogenic agents.

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Variability in glucose transporter-1 levels and hexokinase activity in human melanoma

Cited by 28 publications

References 39 publications

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways

Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers

Angiostatin's molecular mechanism: Aspects of specificity and regulation elucidated

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