Glucose transporter 1 in health and disease

Pragallapati, Sindhuri; Manyam, Ravikanth

doi:10.4103/jomfp.jomfp_22_18

Cited by 68 publications

(47 citation statements)

References 55 publications

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“…Surprisingly, in the present study no statistically significant alterations were observed in GLUT1 + EV levels in the circulation. Although GLUT1 is mainly abundant in BMECs, it is also expressed in erythrocytes [ 42 ] and by BCCs, in primary tumors and in distant metastases [ 43 , 44 ], which may contribute to GLUT1 + EVs release even in basal conditions. Compared to GLUT1, TfR has also been shown to be mainly expressed by BMECs [ 22 ], though not exclusively [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

Figueira

Godinho-Pereira

Galego

et al. 2021

IJMS

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Triple negative breast cancer presents higher mortality and poorer survival rates than other breast cancer (BC) types, due to the proneness to brain metastases formation, which are usually diagnosed at advanced stages. Therefore, the discovery of BC brain metastases (BCBM) biomarkers appears pivotal for a timely intervention. With this work, we aimed to disclose microRNAs (miRNAs) and extracellular vesicles (EVs) in the circulation as biomarkers of BCBM formation. Using a BCBM animal model, we analyzed EVs in plasma by nanoparticle tracking analysis and ascertained their blood-brain barrier (BBB) origin by flow cytometry. We further evaluated circulating miRNAs by RT-qPCR and their brain expression by in situ hybridization. In parallel, a cellular model of BCBM formation, combining triple negative BC cells and BBB endothelial cells, was used to differentiate the origin of biomarkers. Established metastases were associated with an increased content of circulating EVs, particularly of BBB origin. Interestingly, deregulated miRNAs in the circulation were observed prior to BCBM detection, and their brain origin was suggested by matching alterations in brain parenchyma. In vitro studies indicated that miR-194-5p and miR-205-5p are expressed and released by BC cells, endothelial cells and during their interaction. These results highlight miRNAs and EVs as biomarkers of BCBM in early and advanced stages, respectively.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

Figueira

Godinho-Pereira

Galego

et al. 2021

IJMS

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“…Glucose is the obligatory energy source in the brain, and is transported into the brain via GLUT1 ( Bélanger et al, 2011 ; Koch and Weber, 2019 ; Pragallapati and Manyam, 2019 ), where it is converted by PFK, PFK is the first irreversible reaction in glucose-driven glycolysis, playing an important role in the control of the glycolysis pathway ( Nakajima, 1995 ; Moreno-Sánchez et al, 2007 ; Real-Hohn et al, 2010 ). We found that GLUT1 protein levels were increased in Gansu zokor brain under hypoxia II condition, which is consistent with similar hypoxia responses reported in some tumor cells ( Chen et al, 2010 ; Cretenet et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus

et al. 2021

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The Gansu zokor (Eospalax cansus) is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O2) or hypoxia II (6 h at 6.5% O2) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found that hif-1α transcription was upregulated via the mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O2 for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.

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“…Glucose metabolism is one of the most significant steps in regulating cellular and systemic homeostasis and tumor carcinogenesis. Glucose transporter protein families provide glucose uptake from the systemic circulation into the cell (5,13,14). GLUT-1 is the main carrier protein found in many cells responsible for physiological and pathological glucose uptake.…”

Section: Discussionmentioning

confidence: 99%

“…Glucose transporter protein 1 (GLUT-1) is the main carrier protein responsible for physiological and pathological glucose transport. The expression of GLUT-1 increases with the effect of hypoxia and decreased oxidative phosphorylation to meet the increasing energy need of tumor cells for proliferation, invasion, and metastasis (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Glut-1 expression in breast cancer

Okçu¹,

Şen²,

Öztürk³

et al. 2021

TJPATH

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Objective: Numerous studies have been conducted to predict the prognosis of breast cancers. The effect of glucose transporter protein 1 (GLUT-1), the main carrier protein responsible for glucose transport, was investigated in breast cancer patients.Material and Method: 170 patients operated for breast carcinoma were included in this study. We analysed the prognostic significance of GLUT-1 immune-expression in 149 patients without neoadjuvant therapy, and in 21 patients with neoadjuvant therapy.Results: GLUT-1 expression was correlated with poor prognostic factors such as estrogen receptor and progesterone receptor negativity, high Ki-67 proliferation index, and high histological and nuclear grade (p<0.001). GLUT-1 was expressed at a statistically higher rate in invasive ductal carcinomas, compared to invasive lobular carcinomas (p <0.001), and was expressed at a higher rate in luminal B, human epidermal growth factor receptor 2 and triple-negative molecular subtypes compared to luminal A subtype tumors (p <0.001). There was no statistically significant difference between GLUT-1 expression and presence of neoadjuvant therapy. Univariate survival analysis showed high GLUT1 expression was associated with low disease-free survival. Conclusion:GLUT-1 expression was found to be associated with poor pathological prognostic factors in breast carcinoma patients. The results suggest that GLUT-1 expression can be considered as a prognostic marker in breast cancers, and it may be used as a target molecule in personalized treatment approaches.

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Glucose transporter 1 in health and disease

Cited by 68 publications

References 55 publications

MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development

The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus

Glut-1 expression in breast cancer

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