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SPC+ KP vs SPC+ KPG1 tumours

ABSTRACT: Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.

ORGANISM(S): Mus musculus

PROVIDER: GSE138756 | GEO | 2020/06/16

REPOSITORIES: GEO

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PPARaDN KP vs PPARaDN KPG1 tumours

Project description:Glucose transporters are the first and rate-limiting step for cellular glucose usage, which is often exacerbated in tumour cells enabling their growth and proliferation. Although inhibiting glucose metabolism in lung tumours could become an efficient treatment strategy, whether and which glucose transporter(s) should be targeted remains unclear because of their possible functional redundancy, and because other nutrients or transporter-independent metabolic processes including autophagy and macropinocytosis can fuel tumour cell growth in certain contexts. Here we show that glucose transporter Glut1 gene deletion in tumour cells does not impact tumour initiation and only slightly delays progression in a genetically-engineered mouse model of lung adenocarcinoma. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we report the presence of multiple lamellar body-like organelles produced by tumour cells. Glucose-derived biomass accumulates in these organelles, and this accumulation is decreased in Glut1-deficient tumour cells. Ex vivo, tumour cell glycolysis is impaired in absence of Glut1 except in case of strong expression of another glucose transporter, Glut3. We show that Glut3 is dispensable for Glut1 wild-type tumour development. In contrast, their combined deletion diminishes tumour growth and prevents the appearance of big lesions. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma; dual blockade could reach therapeutic responses not achieved by individual targeting.

2020-06-16 | GSE138755 | GEO

KP lung tumours

2020-06-16 | GSE138754 | GEO

CC10+ KP vs CC10+ KPG1 tumours

2020-06-16 | GSE138753 | GEO

Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Project description:Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

| PRJNA577053 | ENA

A Distinct Role for GLUT3 in Glioblastoma Invasion

Project description:In a study of GLUT1 and GLUT3, we used RNA-sequencing to assess the affects of GLUT1 and GLUT3 knockdown in the D456 glioblastoma cell line.

2020-07-01 | GSE148739 | GEO

Expression profiling of lung neutrophils

Project description:Neutrophils are the most abundant circulating leucocytes and constitute an essential component of innate immunity. Although their role in cancer development is still poorly defined, pro- or anti-tumor properties have been attributed to tumor-associated neutrophils (TANs), suggesting major functional diversities. In this study, we focused on the mechanisms involved in neutrophil accumulation within the lung tumor mass. We first identified G-CSF as an inducer of the high-affinity glucose transporter Glut1 in neutrophils, increasing their survival ex vivo. In a genetically engineered mouse model of lung adenocarcinoma, we report that TANs have an increased Glut1 expression and glucose metabolism compared to normal neutrophils. To elucidate the impact of glucose uptake on TANs, we used an in vivo strategy based on two recombinases, Flp to initiate lung tumors, and Cre to delete Glut1 specifically in neutrophils. We demonstrate that the loss of Glut1 decreases the SiglecFhigh TAN subpopulation by accelerating neutrophil turnover in tumors through reduced survival and augmented recruitment. Accelerated TAN turnover led to a decreased tumor growth and synergized with radiotherapy. Altogether, our results demonstrate the importance of Glut1 for neutrophil turnover, which directly affects the pro- versus anti-tumor balance within the tumor. These results also suggest that metabolic vulnerabilities can be exploited to target tumor-supportive neutrophil populations.

2021-03-18 | GSE140153 | GEO

Expression profiling of CD45- lung tumor cells

2021-03-18 | GSE140154 | GEO

Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation

Project description:Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. LC-MS was used to characterize the isolates from cells stimulated with PDGF-BB-conjugated nanoparticles (endocytic vesicle fraction) or PDGF-BB plus unconjugated nanoparticles (control). Taken together, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.

2023-06-19 | MSV000092208 | MassIVE

A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells

Project description:We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to a value that favors cancer progression and metastasis. This is likely in cooperation with the ion transport family. Here, we examined the expression pattern of selected ion transporters, glucose transporters, and carbonic anhydrases in a triple negative cell model of human breast cancer (UFH-001) and the effect of hypoxia. Heat map analysis of RNA transcripts from normoxic and hypoxic cells were significantly different. Additionally, our results show that transcription of the MCT1 monocarboxylate transporter, but not that of MCT4, was sensitive to hypoxia. Both MCT1 and MCT4 were robustly expressed at the protein level, but neither were significantly upregulated by hypoxia. Only low levels of the vATPase and NHE1 transcripts were detected, which is consistent with little to no detectable signal at the protein level. Our data also show high transcript levels of the GLUT1-glucose transporter, CAII and CAIX. Only GLUT1 and CAIX transcription were significantly increased by exposure to hypoxia. CAXII transcripts levels were very low, confirming the lack of expression at the protein level. Yet, CAXII transcription was significantly increased by hypoxia. Overall protein levels of our proteins of interest matched transcription patterns. These studies show a coordinate expression at both the transcriptional and translational levels of the monocarboxylate transporters, the GLUT1 transporter and CAIX in the aggressive triple negative UFH-001 breast cancer cells.

2019-12-01 | GSE123856 | GEO

GLUT3/SLC2A3 is an endogenous marker of hypoxia in prostate epithelial and prostate cancer cells.

Project description:The microenvironment of solid tumors is dynamic and frequently contain pockets of low oxygen levels (hypoxia) surrounded by regions of normal oxygen levels. Indeed, a compromised vascular is a is hallmark of the tumor microenvironment, creating gradients of hypoxia. Notably, hypoxia associates with increased metastasis and poor survival in patients. Therefore, to aid therapeutic decisions and better understand hypoxia's role in cancer progression, it is critical to identify endogenous biomarkers of hypoxia to spatially phenotype oncogenic lesions in human tissue, whether precancerous, benign, or malignant. Here, we characterize the glucose transporter GLUT3/SLC2A3 as a biomarker of hypoxia prostate epithelial cells and prostate tumors. Transcriptomic analyses of hypoxic immortalized prostate epithelial cells revealed a highly significant increase in GLUT3 expression. GLUT3 upregulation was also detected by immunostaining in hypoxic prostate epithelial cells and prostate cancer cell lines. Additionally, GLUT3 dramatically co-localized with the hypoxia-marker pimonidazole in xenograft tumors formed from prostate cancer cells and showed distinct concentration gradients within patient-derived xenograft tumors from primary and metastatic prostate cancer. Compared to established hypoxia-response genes, GLUT1 and CA9, GLUT3 shows a higher degree of hypoxia labeling within tumor tissue and may serve as a alternative endogenous biomarker of hypoxia.

2022-02-16 | GSE196634 | GEO

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