Cholesterol inhibits hepatocellular carcinoma invasion and metastasis by promoting CD44 localization in lipid rafts
Cholesterol inhibits hepatocellular carcinoma invasion and metastasis by promoting CD44 localization in lipid rafts
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胆固醇通过促进CD44在脂筏中的定位抑制肝细胞癌的侵袭和转移
DOI：
10.1016/j.canlet.2018.04.038
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发表时间：
2018
期刊：
影响因子：
9.7
通讯作者：
王红阳
中科院分区：
文献类型：
--
作者：
杨知时;秦文昊;陈瑶;袁波;宋晓玲;王碧波;沈锋;付静;王红阳
胆固醇在调节对细胞功能至关重要的膜蛋白的作用中起着至关重要的作用。血清胆固醇对肝细胞癌（HCC）患者预后的影响尚不明确。在这里，我们报告说，高水平的胆固醇预示着良好的生存和手术后低疾病复发。胆固醇能显著抑制肝癌细胞的迁移和侵袭，抑制肝癌的转移。高水平的胆固醇促进CD 44易位到脂筏中并减弱CD 44-Ezrin结合，这对于细胞迁移和癌症转移至关重要。胆固醇对肝癌转移的抑制作用可通过下调CD 44或其棕榈酰化抑制剂阻断CD 44在脂筏中的定位而被消除。此外，CD 44在脂筏内的滞留明显减弱了HCC的迁移和侵袭，为延长HCC患者的生存期提供了潜在的治疗策略。
Cholesterol plays a vital role in modulating the action of membrane proteins critical to cellular function. The effect of serum cholesterol on the prognosis of hepatocellular carcinoma (HCC) patients remains uncertain. Here, we report that high levels of cholesterol predict good survival and low disease recurrence after surgery. Cholesterol could significantly suppress migration and invasion of HCC cells and restrain metastasis of HCC in mice. High levels of cholesterol promoted CD44 translocation into lipid rafts and attenuated CD44-Ezrin binding, which are crucial for cell migration and cancer metastasis. The suppressive effect of cholesterol on HCC metastasis was abolished by the downregulation of CD44 or its palmitoylation inhibitor, which blocked CD44 localization in lipid rafts. Furthermore, pharmacologically promoting CD44 retention inside lipid rafts obviously attenuated HCC migration and invasion, providing a potential therapeutic strategy to prolong the survival of HCC patients.