ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 278 papers, 5 of them syntheses that pooled it.
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Who cites it
278 citing papers in PubMed, 5 syntheses or guidelines pooled it, 454 citations in OpenAlex.
- The antitumoral effect of statins in pancreatic ductal adenocarcinoma: a scoping review.Frontiers in pharmacology · 2026Pooled it
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Clinical Significance and Immunometabolism Landscapes of a Novel Recurrence-Associated Lipid Metabolism Signature In Early-Stage Lung Adenocarcinoma: A Comprehensive Analysis.Frontiers in immunology · 2022Pooled it
- The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.Frontiers in oncology · 2022Pooled it
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Dyslipidaemias in cancer patients.European heart journal · 2026Review
- Article
- StarD5 Regulates Cholesterol Homeostasis to Promote Colorectal Cancer Progression and the Cancer Stem Cell Phenotype.Molecular cancer research : MCR · 2026Article
- The interplay between lipid metabolism, cancer progression and anti-cancer immunity.Experimental & molecular medicine · 2026Review
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- Identification of serum protein biomarkers for pre-cancerous lesions associated with pancreatic ductal adenocarcinoma.Molecular oncology · 2026Article
- Identification of lipid metabolism-related biomarkers in familial hypercholesterolemia via integrated bioinformatics and machine learning approaches.Journal of cardiothoracic surgery · 2026Article
- METTL7A inhibits progression of colorectal cancer through the SREBP1 / FDFT1 / SQLE / CYP51A1 / cholesterol metabolic pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Integrated analysis of metabolic gene features and the immune microenvironment: identification of DPYD-mediated prognostic model and therapeutic targets in pancreatic cancer.BMC gastroenterology · 2026Article
- Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.Cancer metastasis reviews · 2026Review
- Pan-cancer analysis of cholesterol metabolism reveals the uptake as a modulator of tumor immune features and of the KRAS pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Lipid Droplets in Cancer: New Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
218 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malignant progression of pancreatic ductal adenocarcinoma (PDAC) is accompanied by a profound desmoplasia, which forces proliferating tumor cells to metabolically adapt to this new microenvironment. We established the PDAC metabolic signature to highlight the main activated tumor metabolic pathways. Comparative transcriptomic analysis identified lipid-related metabolic pathways as being the most highly enriched in PDAC, compared with a normal pancreas. Our study revealed that lipoprotein metabolic processes, in particular cholesterol uptake, are drastically activated in the tumor. This process results in an increase in the amount of cholesterol and an overexpression of the low-density lipoprotein receptor (LDLR) in pancreatic tumor cells. These findings identify LDLR as a novel metabolic target to limit PDAC progression. Here, we demonstrate that shRNA silencing of LDLR, in pancreatic tumor cells, profoundly reduces uptake of cholesterol and alters its distribution, decreases tumor cell proliferation, and limits activation of ERK1/2 survival pathway. Moreover, blocking cholesterol uptake sensitizes cells to chemotherapeutic drugs and potentiates the effect of chemotherapy on PDAC regression. Clinically, high PDAC Ldlr expression is not restricted to a specific tumor stage but is correlated to a higher risk of disease recurrence. This study provides a precise overview of lipid metabolic pathways that are disturbed in PDAC. We also highlight the high dependence of pancreatic cancer cells upon cholesterol uptake, and identify LDLR as a promising metabolic target for combined therapy, to limit PDAC progression and disease patient relapse.
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