Fructose transporter Glut5 expression in clear renal cell carcinoma

Villaamil, Vanessa Medina; Gallego, Guadalupe Aparicio; Rubira, L. Valbuena; Campelo, Rosario García; Valladares‐Ayerbes, Manuel; Pulido, Enrique Grande; Bolós, Maria Victoria; Caínzos, I. Santamarina; Aparicio, Luís M. Antón

doi:10.3892/or.2010.1096

Cited by 28 publications

(24 citation statements)

References 62 publications

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“…More recent RNA-seq analyses found human GLUT5 expression in duodenum, bone marrow and kidney [51]. GLUT5 was found to have an association with malignant clear renal cell carcinoma [52]. According to the NCBI Gene database [32,37], orthologs of glut5/slc2a5 are found so far in 123 organisms across chicken, dog, cow, chimpanzee, Rhesus monkey, mouse, rat and X. tropicalis .…”

Section: Glut Transporter Classesmentioning

confidence: 99%

Avian and Mammalian Facilitative Glucose Transporters

2017

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The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1–12 and H+-myo-inositol transporter (HMIT)). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It is clear that there are no chicken orthologs of mammalian GLUT4 and GLUT7. Our examination of GLUT members in the chicken revealed that some chicken GLUT members do not have corresponding orthologs in mammals. We review the information regarding GLUT orthologs and their function and expression in mammals and birds, with emphasis on chickens and humans.

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Section: Glut Transporter Classesmentioning

confidence: 99%

Avian and Mammalian Facilitative Glucose Transporters

2017

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“…However, the authors did not discuss the survival potential of such a mechanism in cancer cells and did not investigate glycogen accumulation as a general characteristic of tumor cells. Finally, we established that RCC cells, in which pVHL is mutated in approximately 50% of cRCC patients (Kaelin, 2009), showed an enlarged cytoplasm due to abnormalities in glycogen and sterol storage (Medina Villaamil et al, 2011). As tumor cells are addicted to glucose and glucose deprivation occurs in parallel to hypoxia, we hypothesized that the decrease in the oxygen level sensed by cancer cells signals energy storage.…”

Section: Introductionmentioning

confidence: 99%

Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

Pelletier¹,

Bellot²,

Gounon³

et al. 2012

Front. Oncol.

171

150

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The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

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“…Previous studies [40] from our group showed that Glut5 expression associates more strongly with the clear cell RCC subtype. The clear cell subtype of RCC is characterised histologically by a distinctive pale, glassy cytoplasm, and this appearance of clear cell RCC is from abnormalities in the carbohydrate and lipid metabolism; these abnormalities result in glycogen and sterol storage.…”

Section: Discussionmentioning

confidence: 77%

Multiple biomarker tissue arrays: A computational approach to identifying protein-protein interactions in the EGFR/ERK signalling pathway

Villaamil¹,

Gallego²,

Valladares‐Ayerbes

et al. 2012

JMS

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BackgroundMany studies have demonstrated genetic and environmental factors that lead to renal cell carcinoma (RCC) and that occur during a protracted period of tumourigenesis. It appears suitable to identify and characterise potential molecular markers that appear during tumourigenesis and that might provide rapid and effective possibilities for the early detection of RCC. EGFR activation induces cell cycle progression, inhibition of apoptosis and angiogenesis, promotion of invasion/metastasis, and other tumour promoting activities. Over-expression of EGFR is thought to play an important role in tumour initiation and progression of RCC because up-regulation of EGFR has been associated with high grade cancers and a worse prognosis.MethodsCharacterisation of the protein profile interacting with EGFR was performed using the following: an immunohistochemical (IHC) study of EGFR, a comprehensive computational study of EGFR protein-protein interactions, an analysis correlating the expression levels of EGFR with other significant markers in the tumourigenicity of RCC, and finally, an analysis of the utility of EGFR for prognosis in a cohort of patients with renal cell carcinoma.ResultsThe cases that showed a higher level of this protein fell within the clear cell histological subtype (p = 0.001). The EGFR significance statistic was found with respect to a worse prognosis. In vivo significant correlations were found with PDGFR-β, Flk-1, Hif1-α, proteins related to differentiation (such as DLL3 and DLL4 ligands), and certain metabolic proteins such as Glut5. In silico significant associations gave us a panel of 32 EGFR-interacting proteins (EIP) using the APID and STRING databases.ConclusionsThis work summarises the multifaceted role of EGFR in the pathology of RCC, and it identifies EIPs that could help to provide mechanistic explanations for the different behaviours observed in tumours.

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Fructose transporter Glut5 expression in clear renal cell carcinoma

Cited by 28 publications

References 62 publications

Avian and Mammalian Facilitative Glucose Transporters

Avian and Mammalian Facilitative Glucose Transporters

Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

Multiple biomarker tissue arrays: A computational approach to identifying protein-protein interactions in the EGFR/ERK signalling pathway

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