Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196634 | GEO | 2022/02/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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

| PRJNA806639 | ENA

A prognostic hypoxia gene signature with low heterogeneity within the dominant tumour lesion in prostate cancer patients.

Project description:Background: Hypoxia gene signatures measured in a biopsy are promising biomarkers in prostate cancer. We determined the ability of a previously developed signature to correctly classify tumours as more or less hypoxic and investigated how intratumour heterogeneity affected its biomarker performance. Methods: The 32-gene signature was determined from gene expression data of 141 biopsies from the dominant (index) lesion of 94 patients treated with prostatectomy. Hypoxic fraction was measured by pimonidazole immunostaining of whole-mount and biopsy sections and used as reference standard for hypoxia. Results: The signature was correlated with hypoxic fraction in whole-mount sections, and the parameters showed almost the same association with tumour aggressiveness. Gene- and pimonidazole-based classification of patients differed considerably. However, the signature had low intratumour heterogeneity compared to hypoxic fraction in biopsies and showed prognostic significance in three independent cohorts. Conclusion: The biopsy-based 32-gene signature from the index lesion reflects hypoxia-related aggressiveness in prostate cancer.

2022-04-01 | GSE178631 | GEO

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

Project description:Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1Î± and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role of Rb in HIF1-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that Rb regulates specific chromosomal gene clusters and loss of Rb in conjunction with hypoxia leads to dysregulation of HIF1-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. RNAs derived from human LNCaP cells stably infected with either scrambled control shRNA or a shRNA directed to RB1. Cells were exposed to either 24 h hypoxia (1% O2) or maintained under normoxic conditions. Biological triplicates were tested and compared.

2016-02-24 | E-GEOD-78245 | biostudies-arrayexpress

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

Project description:Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role of Rb in HIF1-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that Rb regulates specific chromosomal gene clusters and loss of Rb in conjunction with hypoxia leads to dysregulation of HIF1-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies.

2016-02-24 | GSE78245 | GEO

Temporal proteomic analysis unravels the hypoxic response of melanoma cells

Project description:Hypoxia is a common feature in various solid tumors including melanoma. Cancer cells in hypoxic environments are resistant to both chemotherapy and radiation. Hypoxia is also associated with immune suppression. Identification of proteins and pathways that regulate survival of cancer cells in hypoxic environments can reveal potential vulnerabilities that can be exploited to improve efficacy of anti-cancer therapy. We carried out global proteome and phosphoproteome profiling in melanoma cell lines to identify proteins and pathways that are induced by hypoxia. Here, using Orbitrap Fusion Mass Spectrometer for analysis and employing TMT-based quantitation, we report >7,000 proteins and >10,000 phosphosites. As expected, several proteins that are known targets of hypoxia inducible factors (HIFs) were found to be overexpressed in the hypoxic models. In addition, several metabolic enzymes showed altered expression revealing metabolic reprogramming in hypoxic conditions. Phosphoproteomic profiling revealed kinase mediated signaling pathways that are induced in hypoxic conditions. Our data provides a comprehensive view of proteomic and phosphoproteomic alterations in hypoxia and reveals potential mechanisms that regulate cell survival in hypoxic environments. These mechanisms can be targeted to improve therapeutic outcomes in cancer treatment. Further, we identify the 20S proteasome as a putative therapeutic target in melanoma.

2021-05-31 | PXD019832 | Pride

Breast cancer hypoxia secretome LC-MS/MS

Project description:Hypoxia is an important driver of cancer progression, and rapidly growing tumors often result in intratumoral hypoxic regions. Hypoxia is associated with metabolic reprogramming and angiogenesis, resulting in enhanced tumor progression. Here, we aimed to study breast cancer hypoxia responses at the proteomic level, and we wanted to identify differences in protein secretion from luminal-like and basal-like cell lines before and after hypoxia.

2023-06-23 | PXD027136 | Pride

Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts

Project description:Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. To this end, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. When we compared 15 NE versus 33 AdCa PDX samples, we identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of protein and RNA concordance from these tumors revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa. Keywords: Proteomics, phosphoproteomics, Neuroendocrine, Adenocarcinoma, biomarkers, surfaceome, secretome, blood proteins, prostate cancer, patient-derived xenograft

2023-06-09 | MSV000092139 | MassIVE

Hypoxia-mediated stabilization of HIF1A in prostatic intraepithelial neoplasia promotes cell plasticity and malignant progression

Project description:Prostate cancer (PCa) is a leading cause of cancer-related deaths. The slow evolution of precancerous lesions to malignant tumors provides a broad time-frame for preventing PCa. To characterize prostatic intraepithelial neoplasia (PIN) progression, we conducted longitudinal studies on Pten(i)pe-/- mice which recapitulate prostate carcinogenesis in humans. We discovered that early PINs are hypoxic and that hypoxia-inducible factor 1 alpha (HIF1A) signaling is activated in luminal cells, which enhances malignant progression. Luminal HIF1A dampens immune surveillance and drives luminal plasticity leading to the emergence of cells with selective Transglutaminase 2 (TGM2) expression and impaired androgen signaling. Importantly, elevated TGM2 levels in PCa patients are associated with shortened progression-free survival after prostatectomy. Finally, we show that pharmacologically inhibiting HIF1A impairs cell proliferation and induces apoptosis in PINs. Therefore, our study demonstrates that HIF1A is a target for PCa prevention, and that TGM2 is a promising prognostic biomarker of early relapse after prostatectomy.

2022-06-07 | GSE189784 | GEO

TMPRSS2-ERG suppresses PTEN/TP53 alteration-induced cancer lineage plasticity

Project description:Lineage plasticity is a major mechanism driving prostate cancer progression and antiandrogen therapy resistance. Deletions or mutations in phosphatase and tensin homolog (PTEN) and TP53 tumor suppressor genes have been linked to lineage plasticity in prostate cancer. Fusion-driven overexpression of the E-twenty-six transformation specific (ETS)-related gene (ERG), encoding an oncogenic transcription factor, is observed in approximately 50% of all prostate cancers, yet its role in prostate cell lineage determination remains elusive. Here we demonstrate that transgenic expression of prostate cancer-associated ERG blocks Pten and Trp53 mutation-induced decreased expression of Ar and its downstream target genes and loss of luminal epithelial cell identity in the mouse prostate. Integrative analyses of ERG chromatin-immunoprecipitation sequencing (ChIP-seq) and transcriptome data show that ERG suppresses expression of a subset of cell cycle-promoting genes and RB phosphorylation, which in turn causes repression of E2F1-mediated expression of non-epithelial lineage genes. Xenograft studies show that PTEN/TP53 double mutated prostate tumors are responsive to the cyclin-dependent kinase 4 or 6 (CDK4/6) inhibitor palbociclib, but resistant to the AR inhibitor enzalutamide, while ERG/PTEN/TP53 triple-mutated prostate tumors behave completely opposite. Our studies identify ERG and the repressed cell cycle gene signature as intrinsic inhibitors of PTEN/TP53 double mutation-elicited lineage plasticity in prostate cancer. Our findings also suggest that ERG fusion can be utilized as a biomarker to guide the treatment of PTEN/TP53-mutated, RB1-intact prostate cancer with either antiandrogen or anti-CDK4/6 therapies.

2018-05-16 | GSE103871 | GEO

Genome scale analysis of DNA methylation patterns in prostate cancer patient derived xenograft models [EPIC Set 1]

Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays

2023-12-31 | GSE227814 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data