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• W2019622883 abstract "Lipid rafts, plasma membrane microdomains, are important for cell survival signaling and cholesterol is a critical lipid component for lipid raft integrity and function. DHA is known to have poor affinity for cholesterol and it influences lipid rafts. Here, we investigated a mechanism underlying the anti-cancer effects of DHA using a human breast cancer cell line, MDA-MB-231. We found that DHA decreased cell surface levels of lipid rafts via their internalization, which was partially reversed by cholesterol addition. With DHA treatment, caveolin-1, a marker for rafts, and EGFR were colocalized with LAMP-1, a lysosomal marker, in a cholesterol-dependent manner, indicating that DHA induces raft fusion with lysosomes. DHA not only displaced several raft-associated onco-proteins, including EGFR, Hsp90, Akt, and Src, from the rafts but also decreased total levels of those proteins via multiple pathways, including the proteasomal and lysosomal pathways, thereby decreasing their activities. Hsp90 overexpression maintained its client proteins, EGFR and Akt, and attenuated DHA-induced cell death. In addition, overexpression of Akt or constitutively active Akt attenuated DHA-induced apoptosis. All these data indicate that the anti-proliferative effect of DHA is mediated by targeting of lipid rafts via decreasing cell surface lipid rafts by their internalization, thereby decreasing raft-associated onco-proteins via proteasomal and lysosomal pathways and decreasing Hsp90 chaperone function." @default.
• W2019622883 created "2016-06-24" @default.
• W2019622883 creator A5001215159 @default.
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• W2019622883 creator A5015148383 @default.
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• W2019622883 creator A5062480382 @default.
• W2019622883 creator A5066597203 @default.
• W2019622883 creator A5082278031 @default.
• W2019622883 date "2014-01-01" @default.
• W2019622883 modified "2023-10-16" @default.
• W2019622883 title "Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis" @default.
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• W2019622883 doi "https://doi.org/10.1016/j.bbalip.2013.10.006" @default.
• W2019622883 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24120917" @default.
• W2019622883 hasPublicationYear "2014" @default.
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