Cholesterol inhibits hepatocellular carcinoma invasion and metastasis by promoting CD44 localization in lipid rafts

被引：75

作者：

Yang, Zhishi ^{[1
,2
]}

Qin, Wenhao ^{[1
,3
]}

Chen, Yao ^{[1
,3
]}

Yuan, Bo ^{[1
,3
]}

Song, Xiaoling ^{[1
,3
]}

Wang, Bibo ^{[1
,3
]}

Shen, Feng ^{[1
,2
]}

Fu, Jing ^{[1
,3
,4
]}

Wang, Hongyang ^{[1
,3
]}

机构：

[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China

[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg, Shanghai 200438, Peoples R China

[3] Natl Ctr Liver Canc, Shanghai, Peoples R China

[4] Fujian Med Univ, Mengchao Hepatobiliary Hosp, Fuzhou, Fujian, Peoples R China

来源：

CANCER LETTERS | 2018年 / 429卷

基金：

中国国家自然科学基金;

关键词：

Cholesterol; HCC; Metastasis; CD44; Lipid raft; PREOPERATIVE SERUM-CHOLESTEROL; BREAST-CANCER; CELLS; ACCUMULATION; CYTOSKELETON; LEVEL;

D O I：

10.1016/j.canlet.2018.04.038

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2018 Elsevier B.V. All rights reserved.

引用

页码：66 / 77

页数：12

共 40 条

[1] Effect of cholesterol on the lateral nanoscale dynamics of fluid membranes [J].

Armstrong, Clare L. ;

Barrett, Matthew A. ;

Hiess, Arno ;

Salditt, Tim ;

Katsaras, John ;

Shi, An-Chang ;

Rheinstaedter, Maikel C. .

EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, 2012, 41 (10) :901-913

[2] Lipid-rafts remain stable even after ionizing radiation induced disintegration of β1 integrin containing focal adhesions [J].

Babel L. ;

Kruse L. ;

Bump S. ;

Langhans M. ;

Meckel T. .

BMC Research Notes, 10 (1)

[3] X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization [J].

Camp, RL ;

Dolled-Filhart, M ;

Rimm, DL .

CLINICAL CANCER RESEARCH, 2004, 10 (21) :7252-7259

[4] The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics [J].

Cruz, Pedro M. R. ;

Mo, Huanbiao ;

McConathy, Walter J. ;

Sabnis, Nirupama ;

Lacko, Andras G. .

FRONTIERS IN PHARMACOLOGY, 2013, 4

[5] Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis [J].

Das, Akash ;

Brown, Michael S. ;

Anderson, Donald D. ;

Goldstein, Joseph L. ;

Radhakrishnan, Arun .

ELIFE, 2014, 3

[6]

de Duve C, 1971, J Cell Biol, V50, P20

[7] Lipid Raft Association Restricts CD44-Ezrin Interaction and Promotion of Breast Cancer Cell Migration [J].

Donatello, Simona ;

Babina, Irina S. ;

Hazelwood, Lee D. ;

Hill, Arnold D. K. ;

Nabi, Ivan R. ;

Hopkins, Ann M. .

AMERICAN JOURNAL OF PATHOLOGY, 2012, 181 (06) :2172-2187

[8]

European Association for the Study of the Liver European Organisation for Research and Treatment of Cancer, 2012, J HEPATOL AMST, V56, P903

[9] The Membrane-Associated Protein, Supervillin, Accelerates F-Actin-Dependent Rapid Integrin Recycling and Cell Motility [J].

Fang, Zhiyou ;

Takizawa, Norio ;

Wilson, Korey A. ;

Smith, Tara C. ;

Delprato, Anna ;

Davidson, Michael W. ;

Lambright, David G. ;

Luna, Elizabeth J. .

TRAFFIC, 2010, 11 (06) :782-799

[10] The Global Burden of Cancer 2013 Global Burden of Disease Cancer Collaboration [J].

Fitzmaurice, Christina ;

Dicker, Daniel ;

Pain, Amanda ;

Hamavid, Hannah ;

Moradi-Lakeh, Maziar ;

Maclntyre, Michael F. ;

Allen, Christine ;

Hansen, Gillian ;

Woodbrook, Rachel ;

Wolfe, Charles ;

Hamadeh, Randah R. ;

Moore, Ami ;

Werdecker, Andrea ;

Gessner, Bradford D. ;

Te Ao, Braden ;

McMahon, Brian ;

Karimkhani, Chante ;

Yu, Chuanhua ;

Cooke, Graham S. ;

Schwebel, David C. ;

Carpenter, David O. ;

Pereira, David M. ;

Nash, Denis ;

Kazi, Dhruv S. ;

De Leo, Diego ;

Plass, Dietrich ;

Ukwaja, Kingsley N. ;

Thurston, George D. ;

Jin, Kim Yun ;

Simard, Edgar P. ;

Mills, Edward ;

Park, Eun-Kee ;

Catala-Lopez, Ferran ;

DeVeber, Gabrielle ;

Gotay, Carolyn ;

Khan, Gulfaraz ;

Hosgood, H. Dean, III ;

Santos, Itamar S. ;

Leasher, Janet L. ;

Singh, Jasvinder ;

Leigh, James ;

Jonas, Jost B. ;

Sanabria, Juan ;

Beardsley, Justin ;

Jacobsen, Kathryn H. ;

Takahashi, Ken ;

Franklin, Richard C. ;

Ronfani, Luca ;

Montico, Marcella ;

Naldi, Luigi .

JAMA ONCOLOGY, 2015, 1 (04) :505-527

← 1 2 3 4 →