Colonization of distant organs by mechanosensitive tumor cells via generation of stable circulating homotypic clusters
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA667054 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12764813_1.fastq.gz | Fastqsanger.gz | |||
| SRR12764813_2.fastq.gz | Fastqsanger.gz | |||
| SRR12764814_1.fastq.gz | Fastqsanger.gz | |||
| SRR12764814_2.fastq.gz | Fastqsanger.gz | |||
| SRR12764815_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Mechanisms governing cancer metastasis remain poorly understood. Once disseminated tumor cells (DTCs) arrive at a metastatic organ, they remain there, latent, and become seeds of metastasis. However, the clonal composition of DTCs in a latent state remains unclear. Here, we applied high-resolution DNA barcode tracking to a mouse model that recapitulated the metastatic dormancy of head and neck squamous cell carcinoma (HNSCC). We found that clones that had abundant circulating tumor cells (CTCs) but were rare in the primary site dominated DTCs. We obtained a specific subclone that dominated CTCs and subsequent DTCs in lungs and bone marrow. Despite no notable features under static conditions, this clone significantly generated stable cell aggregates that were resistant to anoikis in suspension culture under fluid shear stress conditions. Even as a heterogeneous population, this clone generated almost monoclonal CTC clusters. Via transcriptome analyses, we identified E-cadherin to be indispensable but not sufficient for such stable cell-cell adhesion. Instead, our data indicated that mutual regulation of cortical actin-myosin dynamics according to mechanostress in the cells within each aggregate governed stable adhesion. Furthermore, the gene expression signature of the mechanosensitive clone, which originated clustered CTCs, was associated with locoregional and metastatic recurrence in patients with HNSCC. These results reveal that intrinsically mechanosensitive rare clones in the parental population dominantly colonize distant sites via homotypic CTC cluster formation. This novel clonal selection mechanism based on intrinsic tumor cell mechanosensitivity may lead to promising cancer therapies.
2020-10-03 | GSE158933 | GEO
Project description:Once disseminated tumor cells (DTCs) arrive at a metastatic organ, they remain there, latent, and become seeds of metastasis. However, the clonal composition of DTCs in a latent state remains unclear. Here, we applied high-resolution DNA barcode tracking to a mouse model that recapitulated the metastatic dormancy of head and neck squamous cell carcinoma (HNSCC). We found that clones abundantly circulated peripheral blood dominated DTCs. Through analyses of multiple barcoded clonal lines, we identified specific subclonal population that preferentially generated homotypic circulating tumor cell (CTC) clusters and dominated DTCs. Despite no notable features under static conditions, this population significantly generated stable cell aggregates that were resistant to anoikis under fluid shear stress (FSS) conditions in an E-cadherin-dependent manner. Our data from various cancer cell lines indicated that the ability of aggregate-constituting cells to regulate cortical actin-myosin dynamics governed the aggregates' stability in FSS. The CTC cluster-originating cells were characterized by the expression of a subset of E-cadherin binding factors enriched with actin cytoskeleton regulators. Furthermore, this expression signature was associated with locoregional and metastatic recurrence in HNSCC patients. These results reveal a biological selection of tumor cells capable of generating FSS-adaptive CTC clusters, which leads to distant colonization.
| S-EPMC7969766 | biostudies-literature
Project description:Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites in many organisms. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotype). We generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2Av nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon boundaries. The distribution of homotypic H2A.Z nucleosomes resembles that of salt-soluble nucleosomes and shows evidence of displacement during transcriptional elongation. Homotypic nucleosomes are also depleted downstream of paused polymerases, where salt-soluble nucleosomes are conspicuously depleted. Our results suggest a model whereby H2A.Z enrichment patterns result from different structural interactions within the core of heterotypic and homotypic nucleosomes following disruption during transcriptional elongation. We analyzed two replicates for input, heterotypic and homotypic purifications. We sequenced one library for each of the single H2Av pulldown and 80mM salt soluble samples.
2010-11-01 | E-GEOD-21615 | biostudies-arrayexpress
Project description:Exercise prevents cancer incidence and recurrence, yet the underlying mechanism remains mostly unknown. Here we report that exercise induces a metabolic reprogramming of internal organs, increasing their nutrient demand, thus protecting them against metastatic colonization by limiting nutrient availability to the tumor, which we termed exercise induced metabolic-shield. Proteomic and ex-vivo metabolic-capacity analyses of mice internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active subjects' plasma demonstrated increased carbohydrate utilization following exercise. Further, epidemiological data of a 20-year follow-up of a large human cohort of cancer free participants, revealed that exercise prior to cancer initiation has a modest impact on cancer incidence in low metastatic stages, but significantly reduced the likelihood of highly metastatic cancer as compared to inactive participants. We utilized two exercise protocols, wherein the mice were subjected to exercise either both pre- and post- melanoma injection or only pre-injection. We found that exercise prior to cancer injection significantly protects against metastases in distant organs, regardless of the three melanoma metastases models we used. Mechanistically, ex-vivo inhibition of the mTOR pathway, via rapamycin treatment, reversed the protection from the exercise induced metabolic-shield. Under limited glucose conditions, active stroma consumed significantly more glucose, at the expense of the tumor, as reflected in histology analyses of mice melanoma metastases. Our data suggests that cancers’ metabolic plasticity and the exercise-induced metabolic reprogramming of the stroma are clashing, raising the opportunity to block metastases by challenging cancers’ metabolic needs.
2023-03-11 | PXD035630 | Pride
Project description:Exercise prevents cancer incidence and recurrence, yet the underlying mechanism remains mostly unknown. Here we report that exercise induces a metabolic reprogramming of internal organs, increasing their nutrient demand, thus protecting them against metastatic colonization by limiting nutrient availability to the tumor, which we termed exercise induced metabolic-shield. Proteomic and ex-vivo metabolic-capacity analyses of mice internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active subjects' plasma demonstrated increased carbohydrate utilization following exercise. Further, epidemiological data of a 20-year follow-up of a large human cohort of cancer free participants, revealed that exercise prior to cancer initiation has a modest impact on cancer incidence in low metastatic stages, but significantly reduced the likelihood of highly metastatic cancer as compared to inactive participants. We utilized two exercise protocols, wherein the mice were subjected to exercise either both pre- and post- melanoma injection or only pre-injection. We found that exercise prior to cancer injection significantly protects against metastases in distant organs, regardless of the three melanoma metastases models we used. Mechanistically, ex-vivo inhibition of the mTOR pathway, via rapamycin treatment, reversed the protection from the exercise induced metabolic-shield. Under limited glucose conditions, active stroma consumed significantly more glucose, at the expense of the tumor, as reflected in histology analyses of mice melanoma metastases. Our data suggests that cancers’ metabolic plasticity and the exercise-induced metabolic reprogramming of the stroma are clashing, raising the opportunity to block metastases by challenging cancers’ metabolic needs.
2023-03-11 | PXD035648 | Pride
Project description:Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites in many organisms. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotype). We generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2Av nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon boundaries. The distribution of homotypic H2A.Z nucleosomes resembles that of salt-soluble nucleosomes and shows evidence of displacement during transcriptional elongation. Homotypic nucleosomes are also depleted downstream of paused polymerases, where salt-soluble nucleosomes are conspicuously depleted. Our results suggest a model whereby H2A.Z enrichment patterns result from different structural interactions within the core of heterotypic and homotypic nucleosomes following disruption during transcriptional elongation.
2010-11-01 | GSE21615 | GEO
Project description:Depletion of Apc gene in Cdx2 Gastro ntestinal Cells Facilitates Metastasis of Colorectal Adenocarcinoma Lgr5 Cells to Distant Organs
| PRJNA940975 | ENA
Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
2024-12-19 | GSE266774 | GEO
Project description:Metastasis of breast cancer to other distant organs is fatal to patients. However, few studies have revealed biomarkers associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers such as HER2, ER and PR, in accurately differentiating between distant metastatic breast cancers from non-distant metastatic ones necessitates the development of novel biomarkers. An integrated proteomics approach that combines filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high resolution MS was applied to acquire in-depth proteome data of distant metastatic breast cancer FFPE tissue. Bioinformatics analyses for gene ontology and signaling pathways using differentially expressed proteins (DEPs) were performed to investigate molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and functional capability of biomarker candidates. A total of 9,459 and 8,760 proteins were identified from the pooled sample set and the individual sample set, respectively. Through our stringent criteria, TUBB2A was selected as a novel biomarker. The metastatic functions of the candidate were subsequently validated. Bioinformatics analysis using DEPs were able to characterize the overall molecular features of distant metastasis as well as investigate the differences across breast cancer subtypes. Our study is the first to explore the distant metastatic breast cancer proteome using FFPE tissue. The depth of our dataset enabled the discovery of novel biomarker and the investigation of proteomic characteristics of distant metastatic breast cancer. The distinct molecular features of breast cancer subtypes were also observed. Our proteomic data has important utility as a valuable resource for the research on distant metastatic breast cancer.
2020-06-05 | PXD016061 | Pride
Project description:Homotypic clustering of L1 and B1 repeats organizes 3D genome
| PRJNA509895 | ENA