Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Awakening and Eliminating Dormant Cancer Cells: A Foundation for Resistance Removal and Recurrence-Free Recovery [RNA-seq]

ABSTRACT: Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164428 | GEO | 2024/01/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Awakening and Eliminating Dormant Cancer Cells: A Foundation for Resistance Removal and Recurrence-Free Recovery [ChIP-seq]

Project description:Tumor therapy mainly targets the tumor bulk, but tends to fail to eradicate the small resistant population of dormant cancer cells (DCCs) that enable relapse and/or metastasis beyond therapy. Using chemoradiotherapy resistant assay and SETD4 expression of a histone lysine methyltransferase, DCCs with high capacity of tumor-initiation and tumorsphere formation were isolated from three types of breast tumors. Exogenous DEK, a nuclear protein, activated the DCCs by binding to open chromatin which decreased SETD4, up-regulated the MYC and down-regulated the P53 signaling pathways. DEK-containing exosomes in blood highly correlate with tumor progress and exosomal DEK promotes tumor relapse and metastasis beyond chemoradiotherapy. Beyond activation, these formerly dormant cancer cells lost their chemoradiotherapy resistance. In treatment of DEK-containing exosomes plus chemoradiotherapy in mice, three types of breast tumors were eliminated without recurrence. Prior DCCs reactivation, as triggered by exogenous DEK may provide treatment options that eliminate both metastasis and recurrence potential.

2024-01-07 | GSE164427 | GEO

Awakening and Eliminating Dormant Cancer Cells: A Foundation for Resistance Removal and Recurrence-Free Recovery [ATAC-seq]

2024-01-07 | GSE164426 | GEO

SETD4 marks Quiescent Cancer Stem Cells with Chemoradiotherapy Resistance in Breast Cancer of MMTV-PyMT Mouse

Project description:We isolated quiescent CSCs using chemoradiotherapy resistance assays on tumors of MMTV-PyMT transgenic (specific breast cancer model) mice. We found that quiescent CSCs specifically expressed SETD4 without exception, and beyond activation exhibited high capacity of tumor-initiation in vivo and tumorsphere formation in vitro. Quiescent CSCs expressed high levels of ALDH1 and CD44 and low levels of CD24, that corresponds with their use as breast CSCs markers. Quiescent CSCs were showed to be resistant and able to survive under chemoradiotherapy treatment in either in vivo or in vitro models. Similarly, SETD4 overexpression caused cells extracted from tumors to exhibit clear chemoradiotherapy resistance. Transcriptomic analysis revealed that the molecular processes associated with cellular quiescence included those of DNA damage response and the Wnt/β-catenin signaling pathway. Together with our previous results, these findings showed that SETD4 marks quiescent CSCs and suggest that SETD4-marked quiescent CSCs could be used as key targets in clinical treatment for multiple cancers.

2021-01-24 | GSE165380 | GEO

Proteomics of exosomes derived from cisplatin-induced dormant A549 cells

Project description:Lung cancer is the leading cause of cancer-related deaths worldwide. Chemotherapy kills most cancer cells, however, the residual cells enter into dormant state. The dormant cancer cells can be reactivated under specific circumstances. Tumor-derived exosomes are the main mediators of tumorigenesis. We are aiming to elucidate the roles of exosomes from cisplatin-induced dormant lung cancer cells in the tumor recurrence and metastasis. We performed differential proteome in dormant A549 cell- and A549 cell-derived exosomes.

2022-10-17 | PXD037475 |

ZFP281 ChIP-sequencing of MMTV-Neu early lesion (EL) and primary tumor (PT) spheres

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims identify ZFP281 targets in MMTV-Neu early lesion (EL) and primary tumor (PT) cells

2021-01-26 | GSE165444 | GEO

Inhibition of extracellular vesicle-derived miR-146a-5p decreases the progression of melanoma brain metastasis in vitro and in vivo

Project description:Development of melanoma brain metastasis is caused by an interaction between tumor cells and normal cells in the brain microenvironment. miRNAs delivered by exosomes derived from the tumor cells seem to prime the brain microenvironment, prior to extravasation of tumor cells into the brain. We investigated miRNA in exosomes extracted from normal (astrocytes, melanocytes) and metastatic melanoma cells (brain, skin and lymph node metastasis). We have discovered that miR-146a-5p is an important player in brain metastatic development: this miRNA was highly upregulated in exosomes from melanoma brain metastasis cells, compared to normal cells.

2023-09-29 | E-MTAB-11798 | biostudies-arrayexpress

scRNAseq of MMTV-Neu lung cancer cells in early and late stage

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims to characterize MMTV-Neu early and late lung disseminated cancer cells (DCCs).

2021-01-26 | GSE165459 | GEO

scRNAseq of MMTV-Neu primary site and lung cancer cells in early and late stage

Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims for a general characterization of the MMTV-Neu mouse model (primary site and lung DCCs) in early and late stages of cancer progression.

2021-01-26 | GSE165456 | GEO

SETD4 Cells Contribute to Brain Development and Maintain Adult Stem Cell Reservoir for Neurogenesis

Project description:Cellular quiescence facilitates maintenance of neural stem cells (NSCs) and their subsequent regenerative functions in response to brain injury and aging. However, the specification and maintenance of NSCs in quiescence from embryo to adulthood remains largely unclear. Here, using Set domain-containing protein 4 (SETD4), an epigenetic determinant of cellular quiescence, we mark a small but long-lived NSC population in deep quiescence in the subventricular zone of adult murine brain. Genetic lineage tracing shows that SETD4+ cells appear before neuroectoderm formation and contribute to brain development. In the adult, conditional knock-out of SETD4 resulted in quiescence exit of NSCs, generating newborn neurons in the olfactory bulb and contributing to damage repair. However, long period deletion of SETD4 lead to exhaustion of NSC reservoir or SETD4 overexpression caused quiescence entry of NSCs, leading to suppressed neurogenesis. This study reveals the existence of long-lived deep quiescent NSCs and their neurogenetic capacities beyond activation.

2022-08-25 | GSE200159 | GEO

RNA sequencing of MMTV-Neu early lesion (EL) and primary tumor (PT) spheres

2021-01-26 | GSE165431 | GEO