ArticleLaboratory investigation; a journal of technical methods and pathology2019
Lipid droplet velocity is a microenvironmental sensor of aggressive tumors regulated by V-ATPase and PEDF.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- ATGL-mediated lipid droplet lipolysis promotes collective cell migration in Drosophila.Development (Cambridge, England) · 2026Article
- Lipid and Foam Cell Accumulation as Novel Pathological Features of Benign Prostatic Hyperplasia.The Prostate · 2026Article
- DGAT1 Drives Racially Divergent Fibroblast Activation via ERK1/2-Dependent Tumorigenic Signaling in Prostate Cancer.Cancer research communications · 2026Article
- ATGL-mediated lipid droplet lipolysis promotes collective migration in Drosophila.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in understanding the relationship between lipid metabolism and immune escape in the tumor microenvironment of gastric cancer.Medical review (2021) · 2025Review
- Revealing the ultrastructure of liveOpen biology · 2025Article
- PEDF and Its Role in Metabolic Disease, Angiogenesis, Cardiovascular Disease, and Diabetes.Biomedicines · 2025Review
- Unsupervised self-organising map classification of Raman spectra from prostate cell lines uncovers substratified prostate cancer disease states.Scientific reports · 2025Article
- Metabolic ripple effects - deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment.Disease models & mechanisms · 2024Review
- An Overview on Lipid Droplets Accumulation as Novel Target for Acute Myeloid Leukemia Therapy.Biomedicines · 2023Review
- The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective.Biomolecules · 2023Review
- Cholesterol metabolism and lipid droplet vacuoles; a potential target for the therapy of aggressive lymphoma.Journal of clinical and experimental hematopathology : JCEH · 2022Article
- Lipid metabolism in pancreatic cancer: emerging roles and potential targets.Cancer communications (London, England) · 2022Review
- Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors.Cell death & disease · 2022Article
- Microtubule motor driven interactions of lipid droplets: Specificities and opportunities.Frontiers in cell and developmental biology · 2022Review
- Motility Plays an Important Role in the Lifetime of Mammalian Lipid Droplets.International journal of molecular sciences · 2021Review
- Microenvironmental Factors Modulating Tumor Lipid Metabolism: Paving the Way to Better Antitumoral Therapy.Frontiers in oncology · 2021Review
- Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease.Molecules (Basel, Switzerland) · 2020Review
- Lipid droplet and its implication in cancer progression.American journal of cancer research · 2020Review
- Lipid droplet motility and organelle contacts.Contact (Thousand Oaks (Ventura County, Calif.))Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Lipid droplets (LDs) utilize microtubules (MTs) to participate in intracellular trafficking of cargo proteins. Cancer cells accumulate LDs and acidify their tumor microenvironment (TME) by increasing the proton pump V-ATPase. However, it is not known whether these two metabolic changes are mechanistically related or influence LD movement. We postulated that LD density and velocity are progressively increased with tumor aggressiveness and are dependent on V-ATPase and the lipolysis regulator pigment epithelium-derived factor (PEDF). LD density was assessed in human prostate cancer (PCa) specimens across Gleason scores (GS) 6-8. LD distribution and velocity were analyzed in low and highly aggressive tumors using live-cell imaging and in cells exposed to low pH and/or treated with V-ATPase inhibitors. The MT network was disrupted and analyzed by α-tubulin staining. LD density positively correlated with advancing GS in human tumors. Acidification promoted peripheral localization and clustering of LDs. Highly aggressive prostate, breast, and pancreatic cell lines had significantly higher maximum LD velocity (LDVmax) than less aggressive and benign cells. LDVmax was MT-dependent and suppressed by blocking V-ATPase directly or indirectly with PEDF. Upon lowering pH, LDs moved to the cell periphery and carried metalloproteinases. These results suggest that acidification of the TME can alter intracellular LD movement and augment velocity in cancer. Restoration of PEDF or blockade of V-ATPase can normalize LD distribution and decrease velocity. This study identifies V-ATPase and PEDF as new modulators of LD trafficking in the cancer microenvironment.
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