Adipocyte-derived lipids mediate melanoma progression via FATP proteins
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA473164 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7221110.fastq.gz | Fastqsanger.gz | |||
| SRR7221111.fastq.gz | Fastqsanger.gz | |||
| SRR7221112.fastq.gz | Fastqsanger.gz | |||
| SRR7221113.fastq.gz | Fastqsanger.gz | |||
| SRR7221114.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:We performed RNA-seq on A375 melanoma cells in monoculture or after coculture with adipocytes and identified differentially expressed genes
2018-05-26 | GSE114941 | GEO
Project description:Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface. Among the six FATP/SLC27A family members, melanomas significantly overexpress FATP1/SLC27A1. Melanocyte-specific FATP1 expression cooperates with BRAFV600E in transgenic zebrafish to accelerate melanoma development, an effect that is similarly seen in mouse xenograft studies. Pharmacologic blockade of FATPs with the small-molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. These data demonstrate that stromal adipocytes can drive melanoma progression through FATP lipid transporters and represent a new target aimed at interrupting adipocyte-melanoma cross-talk.Significance: We demonstrate that stromal adipocytes are donors of lipids that mediate melanoma progression. Adipocyte-derived lipids are taken up by FATP proteins that are aberrantly expressed in melanoma. Inhibition of FATPs decreases melanoma lipid uptake, invasion, and growth. We provide a mechanism for how stromal adipocytes drive tumor progression and demonstrate a novel microenvironmental therapeutic target. Cancer Discov; 8(8); 1006-25. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 899.
| S-EPMC6192670 | biostudies-literature
Project description:The goal of this study is to understand the role of adipocyte-specific Trib1 in adiponectin and plasma lipid regulation. Here, we report that adipocyte-specific Trib1 knockout mice (Trib1_ASKO) have increased plasma adiponectin levels and decreased plasma cholesterol and triglycerides. We demonstrate that loss of Trib1 increases adipocyte production and secretion of adiponectin independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice suggests that alterations in adipocyte function underlie the plasma lipid changes observed in these mice. Secretomics and RNA-seq analysis revealed that Trib1_ASKO mice have increased production of Lpl and decreased production of Angptl4 in adipose tissue, and fluorescent substrate assays confirm an increase in adipose tissue Lpl activity, which likely underlies the observed triglyceride phenotype. In summary, we demonstrate here a novel role for adipocyte Trib1 in regulating plasma adiponectin, total cholesterol, and triglycerides in mice, confirming previous genetic associations observed in humans and providing a novel avenue through which Trib1 regulates plasma lipids and coronary artery disease.
2022-06-30 | GSE168596 | GEO
Project description:Lipids play crucial roles in plant-microbe interactions, functioning as structural components, signaling molecules, and microbe-associated molecular patterns (MAMPs); however, the mechanisms underlying lipid perception and signaling pathways in plants remain largely unknown. This study investigates the immune responses triggered in Hordeum vulgare (barley) by lipid extracts from the root endophytic fungus Serendipita indica. We compare these responses to those elicited by the carbohydrate MAMP chitohexaose and the fungal sterol lipid ergosterol, a 5,7-diene oxysterol recognized as a MAMP in plants. Our results demonstrate that S. indica lipid extract induces hallmarks of pattern-triggered immunity (PTI) in barley. Ergosterol was identified as the main immunogenic component and was detected in the apoplastic fluid of S. indica-colonized barley roots. Using a multi-omics approach combining transcriptomics, phosphoproteomics, and metabolomics, our data provide evidence for the activation of phosphatidylinositol phosphate (PIP) signaling and diterpene biosynthesis upon exposure to fungal lipids. Furthermore, we show that phosphatidic acid (PA) enhances lipid-mediated apoplastic reactive oxygen species (ROS) production in barley. These findings indicate that plant lipids mediate immune responses to fungal lipids in barley, advancing our understanding of lipid perception and signaling in plant-microbe interactions.
2025-01-31 | PXD056788 | Pride
Project description:Adipocyte Specific Tribbles1 Regulates Plasma Adiponectin and Plasma Lipids in Mice
| PRJNA708349 | ENA
Project description:For the first time in any system, we generated experiment-matched datasets of the levels of RNAs, proteins, metabolites, and lipids from un-arrested, growing, and synchronously dividing yeast cells.
2019-12-11 | GSE135476 | GEO
Project description:Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are unknown. We show that stromal lipids from young adipocytes are taken up by melanoma cells, and lipids increase melanoma oxidative phosphorylation (OXPHOS) and oxidative stress, which decreases metastatic burden. In contrast, the aged TME provides fewer lipids, leading to lower OXPHOS and higher metastatic capacity. Young adipocytes transfer phosphatidylcholine (PC) to melanoma cells, where PC upregulates PI3K/AKT and mitochondrial OXPHOS. Melanoma cells with high OXPHOS predominantly seed the lung and brain, but do not colonise the liver, and decreasing oxidative stress with antioxidant supplements shifts tropism from the lung to the liver. In contrast, although the aged stroma has fewer total lipids, it has more ceramides, which activate the S1P/STAT3/IL6 signalling axis to direct melanoma liver tropism. Inhibiting OXPHOS in the young stroma and blocking IL6 receptor in the aged stroma reduces the age-specific patterns of metastasis imposed by stromal lipids.
2025-03-26 | GSE292629 | GEO
Project description:Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are unknown. We show that stromal lipids from young adipocytes are taken up by melanoma cells, and lipids increase melanoma oxidative phosphorylation (OXPHOS) and oxidative stress, which decreases metastatic burden. In contrast, the aged TME provides fewer lipids, leading to lower OXPHOS and higher metastatic capacity. Young adipocytes transfer phosphatidylcholine (PC) to melanoma cells, where PC upregulates PI3K/AKT and mitochondrial OXPHOS. Melanoma cells with high OXPHOS predominantly seed the lung and brain, but do not colonise the liver, and decreasing oxidative stress with antioxidant supplements shifts tropism from the lung to the liver. In contrast, although the aged stroma has fewer total lipids, it has more ceramides, which activate the S1P/STAT3/IL6 signalling axis to direct melanoma liver tropism. Inhibiting OXPHOS in the young stroma and blocking IL6 receptor in the aged stroma reduces the age-specific patterns of metastasis imposed by stromal lipids.
2025-03-26 | GSE292628 | GEO
Project description:Cancer cells adapt to signals in the tumor microenvironment (TME), but the TME cues that impact metastasis and tropism are unknown. We show that stromal lipids from young adipocytes are taken up by melanoma cells, and lipids increase melanoma oxidative phosphorylation (OXPHOS) and oxidative stress, which decreases metastatic burden. In contrast, the aged TME provides fewer lipids, leading to lower OXPHOS and higher metastatic capacity. Young adipocytes transfer phosphatidylcholine (PC) to melanoma cells, where PC upregulates PI3K/AKT and mitochondrial OXPHOS. Melanoma cells with high OXPHOS predominantly seed the lung and brain, but do not colonise the liver, and decreasing oxidative stress with antioxidant supplements shifts tropism from the lung to the liver. In contrast, although the aged stroma has fewer total lipids, it has more ceramides, which activate the S1P/STAT3/IL6 signalling axis to direct melanoma liver tropism. Inhibiting OXPHOS in the young stroma and blocking IL6 receptor in the aged stroma reduces the age-specific patterns of metastasis imposed by stromal lipids.
2025-03-26 | GSE292627 | GEO
Project description:Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes promote melanoma aggressiveness through fatty acid oxidation, with a heightened effect in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. Using an adapted SILAC technique, we show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation related enzymes as shown by classical LC-MS/MS analysis. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation after release through lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance in obesity.
2020-01-09 | PXD014487 | Pride