ArticleJournal of experimental & clinical cancer research : CR2022
Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.Biomedicines · 2026Review
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- Multiomic and functional validation of ACSL3, a regulator of fatty acid metabolism, as a lymph node metastasis-associated gene in lung adenocarcinoma.Respiratory research · 2026Article
- A novel PAAoptosis-inducing ERRα-targeting compound for combating hematopoietic and solid cancers.Cell death discovery · 2026Article
- Article
- LncRNA CRCMSL interferes in phospholipid unsaturation to suppress colorectal cancer progression via reducing membrane fluidity.Journal of advanced research · 2025Article
- Estrogen-related receptor alpha mitigates radiation-induced bowel injury through gut enrichment ofGut microbes · 2025Article
- Novel MAFG-METTL14-SCD1 axis regulates lipid metabolism mediating choroidal melanoma distant metastasis.Journal of experimental & clinical cancer research : CR · 2025Article
- Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer.Journal for immunotherapy of cancer · 2025Article
- Identification of biomarkers in gynecologic cancers: a machine learning approach for metabolomics.Translational and clinical pharmacology · 2025Article
- Detecting metabolic signatures in endometrial cancer: potential applications of Raman spectroscopy.Future oncology (London, England) · 2025Review
- FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis.Cell death discovery · 2025Article
- High glucose levels promote glycolysis and cholesterol synthesis via ERRα and suppress the autophagy-lysosomal pathway in endometrial cancer.Cell death & disease · 2025Article
- Expression of AMPK and PLIN2 in the regulation of lipid metabolism and oxidative stress in bitches with open cervix pyometra.BMC veterinary research · 2025Article
- Evaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses.Scientific reports · 2025Article
- The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB.Molecular pharmacology · 2024Article
- Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer.Biomolecules · 2024Article
- Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression.Journal of experimental & clinical cancer research : CR · 2024Article
- Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer.Metabolites · 2024Article
- ERRα: unraveling its role as a key player in cell migration.Oncogene · 2024Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundEstrogen-related receptor α (ERRα) has been reported to play a critical role in endometrial cancer (EC) progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. The transcription factor EB (TFEB)-ERRα axis induces lipid reprogramming to promote progression of EC was explored in this study.
methodsTFEB and ERRα were analyzed and validated by RNA-sequencing data from the Cancer Genome Atlas (TCGA). The TFEB-ERRα axis was assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the TFEB-ERRα-related lipid metabolism pathway. Pseudopods were observed by scanning electron microscope. Furthermore, immunohistochemistry and lipidomics were performed in clinical tissue samples to validate the ERRα-related lipids.
resultsTFEB and ERRα were highly expressed in EC patients and correlated to EC progression. ERRα is the direct target of TFEB to mediate EC lipid metabolism. TFEB-ERRα axis mainly affected glycerophospholipids (GPs) and significantly elevated the ratio of phosphatidylcholine (PC)/sphingomyelin (SM), which indicated the enhanced membrane fluidity. TFEB-ERRα axis induced the mitochondria specific phosphatidylglycerol (PG) (18:1/22:6) + H increasing. The lipid reprogramming was mainly related to mitochondrial function though combining lipidomics and proteomics. The maximum oxygen consumption rate (OCR), ATP and lipid-related genes acc, fasn, and acadm were found to be positively correlated with TFEB/ERRα. TFEB-ERRα axis enhanced generation of pseudopodia to increase the invasiveness. Mechanistically, our functional assays indicated that TFEB promoted EC cell migration in an ERRα-dependent manner via EMT signaling. Consistent with the in vitro, higher PC (18:1/18:2) + HCOO was found in EC patients, and those with higher TFEB/ERRα had deeper myometrial invasion and lower serum HDL levels. Importantly, PC (18:1/18:2) + HCOO was an independent risk factor positively related to ERRα for lymph node metastasis.
conclusionLipid reprogramming induced by the TFEB-ERRα axis increases unsaturated fatty acid (UFA)-containing PCs, PG, PC/SM and pseudopodia, which enhance membrane fluidity via EMT signaling to promote EC progression. PG (18:1/22:6) + H induced by TFEB-ERRα axis was involved in tumorigenesis and PC (18:1/18:2) + HCOO was the ERRα-dependent lipid to mediate EC metastasis.
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