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- W2968754628 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." @default.
- W2968754628 created "2019-08-22" @default.
- W2968754628 creator A5010410306 @default.
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- W2968754628 creator A5090983404 @default.
- W2968754628 date "2019-12-01" @default.
- W2968754628 modified "2023-10-11" @default.
- W2968754628 title "Lipid droplet velocity is a microenvironmental sensor of aggressive tumors regulated by V-ATPase and PEDF" @default.
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- W2968754628 cites W1976719807 @default.
- W2968754628 cites W1992521638 @default.
- W2968754628 cites W2004501853 @default.
- W2968754628 cites W2007917102 @default.
- W2968754628 cites W2011257151 @default.
- W2968754628 cites W2012296410 @default.
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- W2968754628 cites W2022084143 @default.
- W2968754628 cites W2024692400 @default.
- W2968754628 cites W2025979041 @default.
- W2968754628 cites W2030677245 @default.
- W2968754628 cites W2041506421 @default.
- W2968754628 cites W2043609102 @default.
- W2968754628 cites W2045983090 @default.
- W2968754628 cites W2059275312 @default.
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- W2968754628 cites W2121233961 @default.
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- W2968754628 cites W2166910049 @default.
- W2968754628 cites W2194840300 @default.
- W2968754628 cites W2208143356 @default.
- W2968754628 cites W2323982236 @default.
- W2968754628 cites W2345381093 @default.
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- W2968754628 cites W2774444156 @default.
- W2968754628 cites W2782345288 @default.
- W2968754628 cites W2785972152 @default.
- W2968754628 cites W2796022005 @default.
- W2968754628 cites W2796607979 @default.
- W2968754628 cites W2800786048 @default.
- W2968754628 cites W2803612921 @default.
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- W2968754628 cites W2891401626 @default.
- W2968754628 cites W2897683294 @default.
- W2968754628 cites W3020890390 @default.
- W2968754628 cites W309420597 @default.
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- W2968754628 doi "https://doi.org/10.1038/s41374-019-0296-8" @default.
- W2968754628 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7289525" @default.
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- W2968754628 hasPublicationYear "2019" @default.
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