Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dietary serine restriction reduces head and neck cancer cell plasticity through epigenetic changes in the chromatin landscape [RNA-seq]

ABSTRACT: Head and neck cancer with its major subsite, oral squamous cell carcinoma (OSCC), is a devastating malignancy with limited treatment options. Given that recent advances in nutritional interventions have been recognized as potential strategies for targeting cancer, we investigated the role of dietary serine restriction in OSCC cell fate decisions. We now report that human OSCC cells behave like serine auxotrophs, depending on exogenous serine to promote growth and sustain plastic cell states, such as cancer stem cells and cells with EMT features. We show that restriction of serine induces endogenous serine synthesis and generates alpha-ketoglutarate (aKG), a co-substrate for JMJD3 nuclear dioxygenase, which demethylates H3K27me3 and de-represses differentiation genes. This is balanced by the loss of H3K4me3 and inhibition of stemness genes. Likewise, dietary serine restriction inhibits orthotopic OSCC growth in syngeneic mice. Our work provides the basis for including precision nutrition to advance treatments for OSCC patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286464 | GEO | 2026/09/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dietary serine restriction reduces head and neck cancer cell plasticity through epigenetic changes in the chromatin landscape [CUT&RUN]

Project description:Head and neck cancer with its major subsite, oral squamous cell carcinoma (OSCC), is a devastating malignancy with limited treatment options. Given that recent advances in nutritional interventions have been recognized as potential strategies for targeting cancer, we investigated the role of dietary serine restriction in OSCC cell fate decisions. We now report that human OSCC cells behave like serine auxotrophs, depending on exogenous serine to promote growth and sustain plastic cell states, such as cancer stem cells and cells with EMT features. We show that restriction of serine induces endogenous serine synthesis and generates alpha-ketoglutarate (aKG), a co-substrate for JMJD3 nuclear dioxygenase, which demethylates H3K27me3 and de-represses differentiation genes. This is balanced by the loss of H3K4me3 and inhibition of stemness genes. Likewise, dietary serine restriction inhibits orthotopic OSCC growth in syngeneic mice. Our work provides the basis for including precision nutrition to advance treatments for OSCC patients.

2026-09-02 | GSE286465 | GEO

Glucose deprivation promotes de-differentiation in lung adenocarcinoma

Project description:Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction on solid cancers, by glucose transporter blocking or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are not known. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) cells induces de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (aKG), leading to attenuated activity of aKG-dependent histone demethylases and consequent histone hypermethylation. We further show that this de-differentiated and aggressive phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1a (HIF1a). Finally, we identified an HIF1a-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further our knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to metabolic therapies targeting glucose uptake and glycolysis.

2023-04-12 | E-MTAB-11678 | biostudies-arrayexpress

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [RNA-seq III]

Project description:Genetic-driven deregulation of the Wnt pathway is crucial but not sufficient for colorectal cancer (CRC) tumourigenesis. Here, we show that environmental glutamine restriction further augments Wnt signaling in APC mutant intestinal organoids to promote stemness and leads to adenocarcinoma formation in vivo via decreasing intracellular alpha-ketoglutarate (aKG) levels. aKG supplementation is sufficient to rescue low-glutamine induced stemness and Wnt hyperactivation. Mechanistically, we found that aKG promotes hypomethylation of DNA and histone H3K4me3, leading to an upregulation of differentiation-associated genes and downregulation of Wnt target genes, respectively. Using CRC patient-derived organoids and several in vivo CRC tumour models, we show that aKG supplementation suppresses Wnt signaling and promotes cellular differentiation, thereby significantly restricting tumour growth and extending survival. Together, our results reveal how the low glutamine metabolic microenvironment impacts Wnt signaling and identify aKG as a potent antineoplastic metabolite for potential differentiation therapy for CRC patients.

2020-03-23 | GSE140269 | GEO

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [RNA-seq II]

2020-03-23 | GSE140267 | GEO

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [RNA-seq I]

2020-03-23 | GSE140266 | GEO

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [methylation array]

2020-03-23 | GSE140265 | GEO

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [RRBS]

2020-03-23 | GSE140264 | GEO

α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer [exome-seq]

2020-03-23 | GSE140263 | GEO

The role of GCN2 kinase in amino acid dependent longevity and feeding behaviour in Drosophila

Project description:Dietary amino acids restriction extends lifespan in diverse species ranging from flies to mammals. The evolutionarily conserved serine/threonine kinase General Control Nonderepressible 2 (GCN2) is a key sensor of amino acid deficiency and has been implicated in lifespan regulation upon dietary restriction. However, the role of individual essential amino acids (EAA) in modulating organismal lifespan and the underlying molecular mechanisms through which EAA mediate these effects are only partially understood. We generated a novel Drosophila GCN2 null mutant and systematically analyzed its response to individual amino acid deficiency.

2022-06-03 | GSE203210 | GEO

Methylation profiling of oral squamous cell carcinoma (OSCC)

Project description:According to epidemiological studies, a vast majority, approximately 80%~90% of male OSCC patients in Taiwan habitually drink alcohol (A), and chew betel quid (B), and use cigarette (C). To assess the impact of these dietary factors on the epigenome, we conduct a high-throughput screen survey in an oral cancer cohort with exposure of A, B, and C. Results indicate aberrent methylation patterns are prevalent in OSCC patients with ABC risk factors. Genomic DNA was collected from tumor and non-tumor pair-wise samples. These biopsies were obtained from 40 male OSCC patients who regularly drink alcohol, chew areca nut and smoking.

2015-04-01 | E-GEOD-38532 | biostudies-arrayexpress

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