Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enhancer profiling in metastatic cancer [ChIP-Seq]

ABSTRACT: Metastases cause the majority of cancer-related deaths. Yet, the origins of metastatic cancer phenotypes remain poorly understood. Few metastasis-specific driver mutations have been identified [1-3], raising the possibility that metastatic transcriptional programmes may emerge from perturbations in the oncogenic signalling cascades that support the development of primary tumours. Here, using genome-wide histone modification profiling, high-throughput chromatin conformation capture by Hi-C and functional analysis in human-derived metastasis models of renal and breast cancers, we identify transcriptional enhancers that drive metastatic cancer progression. We demonstrate that specific enhancers and enhancer clusters are activated in metastatic cancer cell populations. The activation status of these enhancers is associated with gene expression patterns predictive of poor patient outcome in clinical samples. CRISPRi-mediated inhibition of enhancer activity and genetic ablation of enhancer sequences demonstrated the requirement of metastasis-associated regulatory elements for metastatic colonization in vivo. We further show that metastatic cancer clones co-opt evolutionarily conserved enhancers that converge on shared metastasis driver genes, such as CXCR4. Thus, we provide functional evidence for the requirement of specific enhancers for metastatic colonization and show that metastatic traits can arise through tissue-specific commissioning of distal gene regulatory elements.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98012 | GEO | 2018/06/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Enhancer profiling in metastatic cancer [RNA-Seq]

Project description:Metastases cause the majority of cancer-related deaths. Yet, the origins of metastatic cancer phenotypes remain poorly understood. Few metastasis-specific driver mutations have been identified [1-3], raising the possibility that metastatic transcriptional programmes may emerge from perturbations in the oncogenic signalling cascades that support the development of primary tumours. Here, using genome-wide histone modification profiling, high-throughput chromatin conformation capture by Hi-C and functional analysis in human-derived metastasis models of renal and breast cancers, we identify transcriptional enhancers that drive metastatic cancer progression. We demonstrate that specific enhancers and enhancer clusters are activated in metastatic cancer cell populations. The activation status of these enhancers is associated with gene expression patterns predictive of poor patient outcome in clinical samples. CRISPRi-mediated inhibition of enhancer activity and genetic ablation of enhancer sequences demonstrated the requirement of metastasis-associated regulatory elements for metastatic colonization in vivo. We further show that metastatic cancer clones co-opt evolutionarily conserved enhancers that converge on shared metastasis driver genes, such as CXCR4. Thus, we provide functional evidence for the requirement of specific enhancers for metastatic colonization and show that metastatic traits can arise through tissue-specific commissioning of distal gene regulatory elements.

2018-06-12 | GSE97928 | GEO

Enhancer profiling in metastatic cancer [HiC-seq]

2018-06-12 | GSE99051 | GEO

Positively selected enhancer elements endow tumor cells with metastatic competence

Project description:Metastasis results from a complex set of traits acquired by tumor cells, distinct from those necessary for tumorigenesis. Here, we investigate the contribution of enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic profiling, we identify substantial differences in signature enhancer-histone marks between near-isogenic pairs of high and low lung-metastatic osteosarcoma cells. We term these regions Metastatic Variant Enhancer Loci (Met-VELs). Met-VELs drive coordinated waves of gene expression during metastatic colonization of the lung. Met-VELs cluster non-randomly, indicating that activity of these enhancers and their associated gene targets is positively selected. Osteosarcoma lung metastasis is inhibited by global interruptions of Met-VEL associated gene expression.

2018-01-15 | GSE74230 | GEO

N-glycoprotein capture mass spectrometry identifies candidate substrates of human Fut enzymes

Project description:How disseminated tumor cells (DTCs) engage specific stromal components in distant organs for survival and outgrowth is a critical but poorly understood step of the metastatic cascade. Previous studies have demonstrated the importance of the epithelial-mesenchymal transition (EMT) in promoting the cancer stem cell properties needed for metastasis initiation, while the reverse process of mesenchymal-epithelial transition (MET) is required for metastatic outgrowth. Here we report that this paradoxical requirement for simultaneous induction of both MET and cancer stem cell traits in DTCs is provided by bone vascular niche E-selectin. Using cell surface alkoxyamine-biotinylation and label-free LC-MS/MS, Glg1 was identified as a top candidate Fut3/Fut6-dependent E-selectin ligand. We functionally validated their involvement in the formation of bone metastasis. These findings provide unique insights into the functional role of E-selectin as a component of the vascular niche criticalfor metastatic colonization in bone.

2019-11-13 | PXD012942 | Pride

Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (ChIP-Seq)

Project description:Metastasis is the cause of death for 90% of cancer patients, but little is known about how cancer cells adapt to and colonize new tissue environments. Using clinical samples and primary/metastatic cell lines, we found metastatic colorectal cancer (CRC) cells lose their colon-specific gene transcription program and gain a liver-specific gene transcription program as they metastasize in the liver. We revealed this transcription reprogramming is driven by a reshaped epigenetic landscape of both typical and super-enhancers. Further, we identified FOXA2, a liver-specific transcription factor, plays a key role in this transcription reprogramming and the colonization of metastatic CRC cells in the liver. Notably, this transcription reprogramming is also observed in multiple cancer types. Our data demonstrate that epigenetically reprogrammed tissue-specific transcription promotes metastasis and should be targeted therapeutically.

2020-06-30 | GSE106921 | GEO

Tissue-specific transcription reprogramming promotes liver metastasis of colorectal cancer (RNA-Seq)

2020-06-30 | GSE106920 | GEO

Transcription profiling of human breast cancer metastasis to the brain to identify genes involved

Project description:Brain metastasis is one of the most feared complications of cancer and the most common intracranial malignancy in adults. Its underlying mechanisms remain unknown. From breast cancer patients with metastatic disease we isolated cell populations that aggressively colonize the brain. Transcriptomic analysis of these cells yielded overlapping gene sets whose expression is selectively associated with brain metastasis. The expression of seventeen of these genes in primary breast tumors is associated with brain relapse in breast cancer patients. Some of these genes are also associated with metastasis to lung but not to liver, bone or lymph nodes, providing a molecular basis for the long-observed clinical link between brain and lung metastasis. Among the functionally validated brain metastasis genes, the cyclooxygenase COX-2, the EGFR ligand HB-EGF, and the brain-specific Î±2-6 sialyltransferase ST6GALNAC5 mediate cancer cell passage through the blood-brain barrier. Other brain metastasis genes encode inflammatory factors and brain-specific proteolytic regulators, suggesting a multifaceted program for breast cancer colonization of the brain. Experiment Overall Design: Two different breast cancer cell lines, MDA-MB-231 and freshly isolated pleural effusion CN34 were used in this study. The MDA-MB-231 group contains three biological replicates of the parental, unselected population, and 4 brain metastatic isolates. CN34 contains 2 biological replicates of the parental, unselected population, and 4 brain metastatic isolates. In each case, the parental population was compared to the brain metastatic isolates to identify gene expression changes associated with the brain metastatic phenotype.

2009-05-16 | E-GEOD-12237 | biostudies-arrayexpress

Rhodes2019 - Immune-Mediated theory of Metastasis

Project description:Abstract: Accumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system - as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example - have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed "immune-mediated" theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti- and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor "education" of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the pro-tumor effects of the immune system in metastatic cancer.

2020-03-28 | BIOMD0000000926 | BioModels

MYC enhancer invasion promotes prognostic cancer type-specific gene programs through an epigenetic switch

Project description:The transcription factor MYC is overexpressed in most cancers, where it drives multiple hallmarks of cancer progression. MYC is known to promote oncogenic transcription by binding to active promoters. In addition, MYC has also been shown to invade distal enhancers when expressed at oncogenic levels, but this enhancer binding has been proposed to have low gene-regulatory potential. Here, we demonstrate that MYC enhancer binding directly promotes cancer type-specific gene programs predictive of poor patient prognosis. MYC induces transcription of enhancer RNA through recruitment of RNAPII, rather than regulating RNAPII pause-release as is the case at promoters. This is mediated by MYC-induced H3K9 demethylation by KDM3A and acetylation by GCN5, leading to enhancer-specific BRD4 recruitment through its bromodomains, which facilitates RNAPII recruitment. Thus, we propose that MYC drives prognostic cancer type-specific gene programs by promoting RNAPII recruitment to enhancers through induction of an epigenetic switch.

2023-11-30 | PXD039586 | Pride

Temporal multi-omics identifies LRG1 as vascular instructor of early metastatic colonization.

Project description:Metastasis is the primary cause of cancer-related mortality and the mechanistically least well understood step of the tumor progression cascade. Employing surgical preclinical metastasis models, we show here that small primary tumors reprogram the body’s vascular endothelium to alter systemic homeostasis and to condition the premetastatic niche for metastatic colonization. Endothelial cells thereby serve as an amplifier of tumor-induced instructive signals. The combined endothelial transcriptomic and serum proteomic screen identified the TGFß pathway signaling specifier LRG1 as an early vascular niche instructor of metastatic colonization. Adjuvant LRG1 inhibition to primary tumor-resected mice delayed metastatic growth and increased overall survival. The study has thereby established the premetastatic systems map of primary tumor-induced vascular changes and identified LRG1 as a therapeutic target for metastasis

2022-05-16 | PXD013978 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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