Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Breast Cancer Stem Cells Regulated Phenotypic Equilibrium Drives Tamoxifen Resistance

ABSTRACT: Breast cancers consist of heterogeneous cellular subpopulations that differ in molecular properties and functional attributes. Cancer cells display phenotypic equilibrium between the stem-like and differentiated states during neoplastic homeostasis. The mechanism and functional implications of the subpopulation equilibrium in cancer progression remain largely unknown. Herein, we report that BCSCs secretome conditioned bulk tumor cells developed resistance to anti-endocrine therapy both in vitro and in vivo. IL8 was significantly enriched in BCSCs secretome and blockade of IL8 signaling reversed the tamoxifen resistance induced by BCSCs. The enhanced Wnt/β-catenin signal simultaneously increased the secretion of IL8 in BCSCs, which leads to the seemingly contradictory behaviors of bulk tumor cells. Collectively, our study characterizes the paracrine effects and identifies key molecules secreted by BCSCs, which may become therapeutic vulnerabilities to overcome tamoxifen resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156454 | GEO | 2020/08/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Paracrine Secretion of IL8 by Breast Cancer Stem Cells Promotes Therapeutic Resistance and Metastasis

Project description:Breast cancer stem cells (CSCs) play pivotal roles in cancer therapeutic failure and metastasis. However, it remains indeterminate how CSCs determine the progression of the bulk cancer cell population. Using a co-culture system in vitro and a co-implantation system in vivo, it is demonstrated herein that the breast cancer stem cell (BCSC) secretome rendered the bulk cancer cell population resistant to anti-estrogen and CDK4/6 inhibitor therapy; as well as increased the metastatic burden attributable to bulk cancer cells. Screening of BCSC secretome identified IL8 as a pivotal factor that potentiated ERα activity, endowed tamoxifen resistance and enhanced metastatic burden by regulation of bulk cancer cell behavior. Pharmacological inhibition of IL8 increased the efficacy of fulvestrant and/or palbociclib by reversing tamoxifen resistance and abrogated metastatic burden. Hence, this study has delineated the mechanism by which BCSCs determine the therapeutic response and metastatic of bulk cancer cells; and thereby suggests novel therapeutic strategies to ameliorate breast cancer outcomes.

2022-12-30 | GSE220295 | GEO

Breast Cancer Stem Cells Regulated Phenotypic Equilibrium Drives Tamoxifen Resistance

Project description:Breast Cancer Stem Cells Regulated Phenotypic Equilibrium Drives Tamoxifen Resistance

| PRJNA658009 | ENA

Breast Cancer Stem Cells Regulated Metabolism Remodeling of Bulk Tumor Cells Drives Immune Evasion

Project description:Reprogramming of energy metabolism plays pivotal roles in cancer progression and immune surveillance. Here, we demonstrated that breast cancer cells showed positive feedback enhanced aerobic glycolysis in hypoxia condition. Further investigation suggested that breast cancer stem cells (BCSCs) induced by hypoxia stimulate aerobic glycolysis in bulk tumor cells. Cells cultured with hypoxic tumor cell- or BCSC-secretome exhibited similar gene expression patterns, with global remodeling of metabolism pathways, particularly glycolysis. BCSCs regulated glycolysis promoted breast cancer progression and evasion of immune surveillance. Screening of BCSC secretome identified MIF as a pivotal factor that potentiated glycolysis by increasing the expression of ALDOC. Breast cancer cell–intrinsic MIF depletion inhibited tumor progression and augmented intratumoral cytolytic CD8+ T cells and pro-inflammatory macrophages. Targeting MIF optimized immune checkpoint therapy of breast cancer in both syngeneic mouse models and humanized mouse model. Hence, this study delineates the contribution of BCSC regulated bulk tumor cell glycolysis in immune surveillance; and thereby proposes strategies to optimize immunotherapy in breast cancer.

2023-06-06 | GSE220616 | GEO

Transcriptomic but not genomic variability confers phenotype of breast cancer stem cells

Project description:Background: Breast cancer stem cells (BCSCs) are considered responsible for cancer relapse and drug-resistance. Understanding the identity of BCSCs may open new avenues in breast cancer therapy. Although several discoveries have been made on BCSCs characterization, the factors critical to BCSCs is largely unclear. This study was aimed to determine whether genomic mutation contributes to the acquisition of cancer stem-like phenotype, and to investigate the genetic and transcriptional features of BCSCs. Methods: We detected the potential mutation hotspot regions by using whole genome sequencing on parental cancer cells and derived serial-generation spheroids in increasing order of BCSC frequency, and then performed target deep DNA sequencing in the level of bulk-cell and single-cell. To identify the transcriptional program associated with BCSCs, bulk-cell and single-cell RNA sequencing were performed. Results: By analyzing whole genome sequencing of bulk cells, potential BCSCs associated mutation hotspot regions were detected. Validation by target deep sequencing, in both bulk-cell and single-cell levels, revealed no genetic changes specifically associated with BCSC phenotype. Moreover, single-cell RNA sequencing showed that cancer cells display profound transcriptional variability at the single-cell level that predicts BCSC features. Notably, this transcriptomic variability is enriched in transcription of a number of genes, revealed as BCSC markers. Individuals with breast cancer in a high-risk recurrence group exhibited higher expression of these transcriptomic variabilities, highlighting their clinical significance. Conclusions: Transcriptional variability, not genetic mutations, distinguish BCSCs from non-BCSCs. The identified BCSCs markers can become novel targets for BCSCs.

2018-10-12 | GSE116180 | GEO

Glucose impairs tamoxifen sensitivity modulating CTGF in breast cancer cells

Project description:Metabolic diseases, including type 2 diabetes and obesity are relevant negative prognostic factor in patients with breast cancer (BC). We have investigated the mechanisms through which elevated glucose levels affect tamoxifen sensitivity of estrogen receptor positive (ER+) BC cells. We found that MCF7 BC cell sensitivity to tamoxifen was 2-fold reduced in 25mM glucose (HG), a concentration mimicking hyperglycaemia, compared to 5.5 mM glucose (LG), resembling normal fasting glucose levels in humans. Shifting MCF7 cells from HG to LG ameliorated their responsiveness to tamoxifen. RNA-Sequencing revealed that glucose modified the transcriptome of MCF7 cells. In particular, cell cycle-related genes were affected by glucose. Combining gene specific knockdown and treatment with human recombinant proteins, we identified the Connective Tissue Growth Factor (CTGF) as glucose-induced factor able to reduce MCF7 cell sensitivity to tamoxifen. Moreover, we found that both CTGF expression levels and tamoxifen responsiveness were enhanced co-culturing MCF7 cells with human adipocytes through an Interleukin-8 (IL8)-mediated mechanism. Indeed, IL8 inhibition reduced CTGF levels and rescued tamoxifen sensitivity in MCF7 cells. Interestingly, CTGF immuno-detection in bioptic specimens obtained from women with ER+ BC correlated with distant metastases (P-value = 0.000), hormone therapy resistance (P-value = 0.000), reduced overall (P-value = 0.051) and disease free survival (P-value = 0.000). Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting the adipocytes’ release of IL8. Both CTGF and IL8 may represent potential targets in novel therapeutic strategies to increase tamoxifen sensitivity.

2017-07-01 | GSE97647 | GEO

IFNγ is a central node in cancer immune equilibrium

Project description:IFNγ is a central node in cancer immune equilibrium

| PRJNA923377 | ENA

IFNγ is a central node in cancer immune equilibrium

Project description:IFNγ is a central node in cancer immune equilibrium

| PRJNA877607 | ENA

ATAD2 maintains the equilibrium between nucleosome assembly and disassembly

Project description:ATAD2 maintains the equilibrium between nucleosome assembly and disassembly

| PRJNA739885 | ENA

IL-12 Virotherapy Induces Immune Equilibrium in Melanoma That is Overcome by Blockade of Innate Inflammatory Cytokine

Project description:Viral vectors deliver therapeutic cargo with the natural adjuvant effect of a pathogen. We engineered a non-replicating herpes simplex virus 1, d106S-IL12, to deliver IL-12 to the tumor microenvironment, resulting in a type I interferon response, rapid production of T cell recruiting chemokines, and accumulation of melanoma-specific CD8 T cells. We immunologically defined a long-term, stable immune equilibrium, whereby mice neither succumbed nor fully cleared their tumors. We profiled the immune equilibrium induced by d106S-IL12, identifying blockade of innate inflammatory cytokines, TNFα, IL-1β, or IL-6 as possible synergistic interventions. Single-cell RNA-sequencing demonstrated that d106S-IL12 induced a loss of Tregs and a shift towards Th1 responses, while blockade of inflammatory cytokines repolarized macrophages towards a less suppressive phenotype. Blockade of each cytokine resulted in downregulation of overlapping inflammatory pathways, shifting immune equilibrium towards tumor clearance. These results suggest targeting innate inflammatory cytokines could enhance immunotherapy efficacy while potentially mitigating toxicity.

2023-07-18 | GSE160132 | GEO

Non-equilibrium pronucleus histones require gametal factor Lsm1 induced major satellite RNA decay

Project description:The development of a multicellular organism with various organs and tissues is a complex but highly concerted process, in which cells acquire different identities through exquisite spatiotemporal regulations called cell fate decision. Here, we Lsm1 targets non-coding major satellite RNAs in mouse zygote, which is required for the non-equilibrium epigenetic modification, especially H3K9me3 establishment during early embryo development.

2022-07-05 | GSE179556 | 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