Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents
Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents
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DOI：
10.2353/ajpath.2006.050959
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发表时间：
2006-04-01
影响因子：
6
通讯作者：
Kim, YN
中科院分区：
文献类型：
--
作者：
Li, YC;Park, MJ;Kim, YN
脂筏/小窝是调节各种细胞功能（包括细胞存活）的信号分子的膜平台。为了更好地理解筏在肿瘤进展和治疗中的作用，我们研究了筏破坏对细胞活力的影响，并比较了人类癌细胞系与正常细胞系中的筏水平。在这里，我们报告使用甲基-β环糊精胆固醇消耗引起失巢凋亡样细胞凋亡，这在A431细胞中涉及筏水平降低，Bcl-xL下调，caspase-3激活，Akt失活，而不管表皮生长因子受体激活。胆固醇补充补充筏上的细胞表面和恢复Akt激活和细胞活力。此外，乳腺癌和前列腺癌细胞系含有更多的脂筏，对胆固醇消耗诱导的细胞死亡比正常细胞更敏感。这些结果表明，癌细胞含有增加水平的筏，并建议筏调节剂作为抗癌药物的潜在用途。
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.