Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling_Medium and long chain fatty acids

ABSTRACT:

Upon penetrating the basement membrane, breast cancer cells directly interact with their surrounding adipose tissue, which forms a unique tumor-associated adipose microenvironment (TAME). However, the underlying mechanism involved in the regulation of lipid metabolic remodeling in the TAME remains elusive. Herein, we identified a Zeb1-orchestrated bidirectional communication between breast cancer cells and their adjacent cancer-associated adipocytes (CAAs). At the molecular level, breast cancer cells, through the secretion of adrenomedullin (AM), induce downregulation of Zeb1 expression to activate the Atgl/Hsl/Scd-depedent lipolysis in CAAs, which subsequently results in the release of palmitoleic acid (POA) into the TAME. In turn, accumulated POA triggers the malignant growth and metastasis of breast cancer cells and their production of AM via an ARA-PDG2-mediated membrane phospholipid replacement mechanism. Importantly, disruption of Zeb1-dependent lipolytic activity and/or membrane phospholipid remodeling within the TAME, severely diminishes the aggressiveness of breast cancer in vitro and in vivo.

INSTRUMENT(S): Gas Chromatography MS - positive

PROVIDER: MTBLS12290 | MetaboLights | 2025-04-30

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	CAAZeb1-off-1.D.zip	Other
	CAAZeb1-off-2.D.zip	Other
	CAAZeb1-off-3.D.zip	Other
	CAAZeb1-off-4.D.zip	Other
	CAAZeb1-off-5.D.zip	Other

Items per page:

1 - 5 of 16

Similar Datasets

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling_Medium and long chain fatty acids_four group

Project description:<p>Upon penetrating the basement membrane, breast cancer cells directly interact with their surrounding adipose tissue, which forms a unique tumor-associated adipose microenvironment (TAME). However, the underlying mechanism involved in the regulation of lipid metabolic remodeling in the TAME remains elusive. Herein, we identified a Zeb1-orchestrated bidirectional communication between breast cancer cells and their adjacent cancer-associated adipocytes (CAAs). At the molecular level, breast cancer cells, through the secretion of adrenomedullin (AM), induce downregulation of Zeb1 expression to activate the Atgl/Hsl/Scd-depedent lipolysis in CAAs, which subsequently results in the release of palmitoleic acid (POA) into the TAME. In turn, accumulated POA triggers the malignant growth and metastasis of breast cancer cells and their production of AM via an ARA-PDG2-mediated membrane phospholipid replacement mechanism. Importantly, disruption of Zeb1-dependent lipolytic activity and/or membrane phospholipid remodeling within the TAME, severely diminishes the aggressiveness of breast cancer in vitro and in vivo.</p>

2025-04-30 | MTBLS12291 | MetaboLights

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling

2025-04-30 | MTBLS12286 | MetaboLights

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling_untargeted metabolites_Lipidomics

2025-04-30 | MTBLS12289 | MetaboLights

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling

2025-04-30 | MTBLS12405 | MetaboLights

Adipocyte-specific Zeb1 confers breast cancer progression by triggering the tumor-associated adipose microenvironment remodeling_Lipidomics_amino

2025-04-30 | MTBLS12287 | MetaboLights

Inhibition of PPARg by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells

Project description:Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes (CAAs) promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction (SVF) of the visceral fat has not. Importantly, we found the derivate of the potent PPARg antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that higher PPARg expression was associated with poorer overall survival of breast cancer patients, and further study showed that BZ26 bound and inhibited PPAR by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARg activity that is capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

2023-08-09 | GSE240082 | GEO

GNPS - The adipose microenvironment dysregulates the mammary myoepithelial cells and could participate to the progression of breast cancer

Project description:Overweight and obesity are now recognized as established risk factors for breast cancer in postmenopausal women. Reciprocal interactions have been described between adipose and cancer cells. Among the cell types present in the breast, myoepithelial cells (MECs) are considered "tumour suppressor" cells. During the transition from ductal carcinoma in situ to invasive cancer, disorganization or even the disappearance of MECs is observed. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition of in situ to invasive carcinoma, particularly in obese patients. Through a co-culture model, we found that adipose cells could decrease the viability of the MECs. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumour suppressor status of MECs and promote the transition from in situ to invasive carcinoma.

2020-11-24 | MSV000086515 | GNPS

Ion Torrent RNA-sequencing of exosomes isolated from ovarian cancer cells, fibroblasts and adipocytes

Project description:We used next-generation sequencing to identify differential microRNA (miRNA) signatures in exosomes isolated from ovarian cancer cells and ovarian cancer-associated fibroblasts (CAFs) and adipocytes (CAAs). We found that a significantly higher levels of miR21 isomiRNAs in exosomes isolated from CAFs and CAAs than in those from ovarian cancer cells.

2016-03-21 | GSE77318 | GEO

ZEB1-regulated inflammatory phenotype in breast cancer cells

Project description:ZEB1-regulated inflammatory phenotype in breast cancer cells

| PRJNA350678 | ENA

Thioridazine induce phospholipid accumulation and necroptosis in breast cancer cells

Project description:An antipsychotic drug, Thioridazine has been shown to inhibit a broad spectrum of cancer cells. However, its molecular mechanism is still not well understood. In the present study, we have shown that thioridazine induces cytostatic effects in both parental and tamoxifen-resistant cancer cells through cell viability, cell count, caspase activation, cell cycle analysis and enhanced p21 levels. Further, using the pharmacometabolomics approach, we identified that thioridazine induces phospholipids accumulation in breast cancer cells. We proved that thioridazine induces only phospholipids accumulation and not neutral lipids in cells by using lipid-specific fluorescent quantification and image analysis. The accumulation of phospholipid induces necroptosis, which was assessed by propidium iodide uptake assay. Thioridazine activates RIP1 and RIP3 signalling and subsequent translocation of pore-forming MLKL to the plasma membrane to initiate necroptosis induction. The MLKL-induced membrane pores were confirmed using a scanning electron microscope cell surface visualization. Further, thioridazine co-treatment enhances the efficacy of tamoxifen in resistant breast cancer cells potentiating its usefulness for combinatorial treatment

2025-02-20 | MTBLS11870 | MetaboLights