ArticleTheranostics2019
Targeting lipid metabolism to overcome EMT-associated drug resistance via integrin β3/FAK pathway and tumor-associated macrophage repolarization using legumain-activatable delivery.
Article in Theranostics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 211 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 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
- P. gingivalis-host interactions direct antibiotic adjuvants for periodontitis antimicrobial therapy.International journal of oral science · 2026Article
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Innovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics.Discover oncology · 2026Review
- Discovery of a potent and orally bioavailable type Ⅰ PRMTs inhibitor for triple-negative breast cancer treatment.Acta pharmacologica Sinica · 2026Article
- Association of statin use with pathological complete response in postmenopausal patients with hormone receptor-positive breast cancer.Scientific reports · 2026Article
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Immunometabolic programming of macrophages and tumor-associated macrophages: metabolic pathways shaping polarization, immune regulation, and disease outcomes.Frontiers in immunology · 2026Review
- Surface-Modified Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a New Perspective for Prostate Cancer Therapy.Nanotechnology, science and applications · 2026Article
- Multi-trait association analysis reveals shared genetic architecture between lung cancer and cardiometabolic diseases.iScience · 2025Article
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- The interplay between extracellular matrix remodeling and cellular lipid metabolic reprogramming in cancer: a review.Molecular biology reports · 2025Review
- Minimal Residual Disease in Breast Cancer: Tumour Microenvironment Interactions, Detection Methods and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- Polyphyllin H Reverses Paclitaxel Resistance in Breast Cancer by Binding Membrane Cholesterol to Inhibit Both ABCB1 and ABCC3.Pharmaceuticals (Basel, Switzerland) · 2025Article
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Nanotherapeutic strategies exploiting biological traits of cancer stem cells.Bioactive materials · 2025Review
- Comprehensive analysis of cholesterol metabolism-related genes in prostate cancer: integrated analysis of single-cell and bulk RNA sequencing.Discover oncology · 2025Article
84 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) is closely associated with the development of drug resistance. Lipid metabolism plays an important role in EMT. This work was to study the cholesterol-lowering drug simvastatin for reversing EMT-associated resistance to chemotherapy via lipid metabolism.
methodsThe combination of simvastatin and paclitaxel was used to overcome the EMT-associated drug resistance. For dual-action on both cancer cells and tumor-associated macrophages (TAM), the tumor microenvironment-activatable multifunctional liposomes were developed for drug codelivery. The liposomes were modified with a hairpin-structured, activatable cell-penetrating peptide that is specifically responsive to the tumor-associated protease legumain.
resultsIt was revealed simvastatin can disrupt lipid rafts (cholesterol-rich domains) and suppress integrin-β3 and focal adhesion formation, thus inhibiting FAK signaling pathway and re-sensitizing the drug-resistant cancer cells to paclitaxel. Furthermore, simvastatin was able to re-polarize tumor-associated macrophages (TAM), promoting M2-to-M1 phenotype switch via cholesterol-associated LXR/ABCA1 regulation. The repolarization increased TNF-α, but attenuated TGF-β, which, in turn, remodeled the tumor microenvironment and suppressed EMT. The liposomal formulation achieved enhanced treatment efficacy.
conclusionThis study provides a promising simvastatin-based nanomedicine strategy targeting cholesterol metabolism to reverse EMT and repolarize TAM to treat drug-resistant cancer. The elucidation of the molecular pathways (cholesterol/lipid raft/integrin β3/FAK and cholesterol-associated LXR/ABCA1 regulation) for anti-EMT and the new application of simvastatin should be of clinical significance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.