Targeting metastasis stem cells through the fatty acid receptor CD36
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ABSTRACT:
PROVIDER: PRJNA295964 | ENA |
REPOSITORIES: ENA
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Project description:Metastasis is the leading cause of cancer-related deaths. For most human cancers, the identity of the cells that initiate and promote metastasis is still unknown, hampering our ability to develop therapies to prevent or inhibit the spread of tumour cells to distant sites. Using an orthotopic model of human oral squamous cell carcinoma (OSCC), we have now identified a subpopulation of CD44bright cells within the primary lesion with the highest potential to develop lymph node and lung metastasis. This population is slow-cycling, expresses high levels of the receptor CD36 at the cell membrane and relies on fatty acid metabolism to thrive in lymph nodes and bronchoalveolar environments. Importantly, inhibition of CD36 by either shRNA or neutralizing monoclonal antibodies severely impairs metastatic spread of primary OSCC patient samples and established cell lines. Further underscoring its importance, CD36 overexpression in poorly disseminating tumours confers an aggressive metastatic behaviour. Analyses of public gene expression data indicate that the presence of the signature-defining CD36+ cells also strongly correlates with a poor prognosis in patients with lung SCC, ovarian cancer, bladder cancer, or luminal breast cancer. By identifying metastasis-promoting cells and then targeting them with CD36 inhibition, novel anti-metastatic therapies could be developed for patients with these types of tumours.
2016-12-16 | GSE83276 | GEO
Project description:Metastasis is the leading cause of cancer-related deaths. For most human cancers, the identity of the cells that initiate and promote metastasis is still unknown, hampering our ability to develop therapies to prevent or inhibit the spread of tumour cells to distant sites. Using an orthotopic model of human oral squamous cell carcinoma (OSCC), we have now identified a subpopulation of CD44bright cells within the primary lesion with the highest potential to develop lymph node and lung metastasis. This population is slow-cycling, expresses high levels of the receptor CD36 at the cell membrane and relies on fatty acid metabolism to thrive in lymph nodes and bronchoalveolar environments. Importantly, inhibition of CD36 by either shRNA or neutralizing monoclonal antibodies severely impairs metastatic spread of primary OSCC patient samples and established cell lines. Further underscoring its importance, CD36 overexpression in poorly disseminating tumours confers an aggressive metastatic behaviour. Analyses of public gene expression data indicate that the presence of the signature-defining CD36+ cells also strongly correlates with a poor prognosis in patients with lung SCC, ovarian cancer, bladder cancer, or luminal breast cancer. By identifying metastasis-promoting cells and then targeting them with CD36 inhibition, novel anti-metastatic therapies could be developed for patients with these types of tumours.
2016-12-16 | GSE72938 | GEO
Project description:Metastasis is the leading cause of cancer-related deaths. For most human cancers, the identity of the cells that initiate and promote metastasis is still unknown, hampering our ability to develop therapies to prevent or inhibit the spread of tumour cells to distant sites. Using an orthotopic model of human oral squamous cell carcinoma (OSCC), we have now identified a subpopulation of CD44bright cells within the primary lesion with the highest potential to develop lymph node and lung metastasis. This population is slow-cycling, expresses high levels of the receptor CD36 at the cell membrane and relies on fatty acid metabolism to thrive in lymph nodes and bronchoalveolar environments. Importantly, inhibition of CD36 by either shRNA or neutralizing monoclonal antibodies severely impairs metastatic spread of primary OSCC patient samples and established cell lines. Further underscoring its importance, CD36 overexpression in poorly disseminating tumours confers an aggressive metastatic behavior. Analyses of public gene expression data indicate that the presence of the signature-defining CD36+ cells also strongly correlates with a poor prognosis in patients with lung SCC, ovarian cancer, bladder cancer, or luminal breast cancer. By identifying metastasis-promoting cells and then targeting them with CD36 inhibition, novel anti-metastatic therapies could be developed for patients with these types of tumours.
2016-12-16 | GSE72935 | GEO
Project description:Metastasis is the leading cause of cancer-related deaths. For most human cancers, the identity of the cells that initiate and promote metastasis is still unknown, hampering our ability to develop therapies to prevent or inhibit the spread of tumour cells to distant sites. Using an orthotopic model of human oral squamous cell carcinoma (OSCC), we have now identified a subpopulation of CD44bright cells within the primary lesion with the highest potential to develop lymph node and lung metastasis. This population is slow-cycling, expresses high levels of the receptor CD36 at the cell membrane and relies on fatty acid metabolism to thrive in lymph nodes and bronchoalveolar environments. Importantly, inhibition of CD36 by either shRNA or neutralizing monoclonal antibodies severely impairs metastatic spread of primary OSCC patient samples and established cell lines. Further underscoring its importance, CD36 overexpression in poorly disseminating tumours confers an aggressive metastatic behaviour. Analyses of public gene expression data indicate that the presence of the signature-defining CD36+ cells also strongly correlates with a poor prognosis in patients with lung SCC, ovarian cancer, bladder cancer, or luminal breast cancer. By identifying metastasis-promoting cells and then targeting them with CD36 inhibition, novel anti-metastatic therapies could be developed for patients with these types of tumours.
2016-12-16 | GSE83346 | GEO
Project description:Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multi-ligand receptor cluster of differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs and parenchymal cells such as myocytes and adipocytes. Whether tissue uptake of FAs is dependent on EC or parenchymal cell CD36, or both, is unknown. Using a cell-specific deletion approach, we show that CD36-mediated FA transport across ECs rate-limits tissue FA uptake, and its loss leads to metabolic effects in parenchymal cells.
2018-06-28 | GSE116350 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with limited treatment options. Here, we demonstrate that fucoxanthin (FUCO), a natural marine carotenoid, ameliorates MASH by targeting the EGR2-CD36 axis. In FFA-induced hepatocyte models (HepG2, Hep3B, and AML12), FUCO significantly reduced lipid accumulation and inflammatory markers without cytotoxicity. Mechanistic studies revealed that FUCO specifically inhibited fatty acid uptake and transport by downregulating CD36, while TG degradation remained unaffected. RNA sequencing identified EGR2 as a master regulator induced by FFA and suppressed by FUCO. Functional validation showed that EGR2 overexpression completely blocked FUCO's lipid-lowering effects and restored CD36 expression, confirming that FUCO acts through EGR2-dependent CD36 inhibition. Bioinformatic analysis further supported EGR2-mediated regulation of CD36 via TNF and SREBF pathways. Collectively, our findings establish EGR2 as a critical molecular target for FUCO and provide mechanistic insights supporting its clinical development for MASH therapy.
2026-08-05 | GSE326385 | GEO
Project description:Adipose tissue is a key pharmacological target to prevent or treat the consequences of obesity. Adipose specific cell surface proteins are especially interesting due to their important roles in orchestrating cellular responses to environmental cues. Nutritionally-regulated adipose and cardiac enriched protein (Nrac) is a small adipocyte specific transmembrane protein with no known function. We show that Nrac modulates CD36 mediated fatty acid uptake, by forming a complex with CD36 and caveolin-1 under low extracellular fatty acid concentrations. Upon loss of Nrac or an increase in extracellular fatty acid levels, leading to reduced Nrac surface localization, CD36 dissociates from caveolin-1 and is internalized via clathrin mediated endocytosis. This results in increased fatty acid uptake into adipocytes, adipocyte hypertrophy, increased fat mass and elevated lipid clearance from the blood in chow diet fed mice. Thus, we unravel a novel regulatory mechanism of adipocyte fatty acid uptake dependent on its extracellular availability
2025-08-04 | PXD054842 | Pride
Project description:Endothelial Cell CD36 Optimizes Tissue Fatty Acid Uptake
| PRJNA478230 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-12-16 | GSE72939 | GEO
Project description:Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examined how ECs transfer FAs. FA interaction with apical membrane CD36 induced Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Fission of the caveolae yielded vesicles containing FAs, CD36 and ceramide that were secreted basolaterally as small (80-100nm) exosome-like extracellular vesicles (sEVs). We visualized EC transfer of FAs in sEVs to underlying myotubes in transwells. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulated circulating FAs in emGFP-labeled puncta. The FA-sEV pathway was mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduced muscle FA uptake, raised circulating FAs, which remained in blood vessels, and lowered glucose, mimicking prominent Cd36-/- phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.
2023-07-02 | GSE235988 | GEO