Cholesterol metabolism in cancer: mechanisms and therapeutic opportunities

被引：641

作者：

Huang, Binlu ^{[1
]}

Song, Bao-Liang ^{[2
]}

Xu, Chenqi ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Shanghai Sci Res Ctr, Shanghai, Peoples R China

[2] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan, Peoples R China

来源：

NATURE METABOLISM | 2020年 / 2卷 / 02期

关键词：

STATIN USE; HEPATOCELLULAR-CARCINOMA; MEVALONATE METABOLISM; PROSTATE-CANCER; DENDRITIC CELLS; ER STRESS; T-CELLS; ACTIVATION; RECEPTORS; INHIBITION;

D O I：

10.1038/s42255-020-0174-0

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cholesterol metabolism produces essential membrane components as well as metabolites with a variety of biological functions. In the tumour microenvironment, cell-intrinsic and cell-extrinsic cues reprogram cholesterol metabolism and consequently promote tumourigenesis. Cholesterol-derived metabolites play complex roles in supporting cancer progression and suppressing immune responses. Preclinical and clinical studies have shown that manipulating cholesterol metabolism inhibits tumour growth, reshapes the immunological landscape and reinvigorates anti-tumour immunity. Here, we review cholesterol metabolism in cancer cells, its role in cancer progression and the mechanisms through which cholesterol metabolites affect immune cells in the tumour microenvironment. We also discuss therapeutic strategies aimed at interfering with cholesterol metabolism, and how the combination of such approaches with existing anti-cancer therapies can have synergistic effects, thus offering new therapeutic opportunities.

引用

页码：132 / 141

页数：10

共 129 条

[21] Squalene epoxidase as a promising metabolic target in cancer treatment [J].

Cirmena, Gabriella ;

Franceschelli, Paola ;

Isnaldi, Edoardo ;

Ferrando, Lorenzo ;

De Mariano, Marilena ;

Ballestrero, Alberto ;

Zoppoli, Gabriele .

CANCER LETTERS, 2018, 425 :13-20

[22] Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients [J].

Condamine, Thomas ;

Dominguez, George A. ;

Youn, Je-In ;

Kossenkov, Andrew V. ;

Mony, Sridevi ;

Alicea-Torres, Kevin ;

Tcyganov, Evgenii ;

Hashimoto, Ayumi ;

Nefedova, Yulia ;

Lin, Cindy ;

Partlova, Simona ;

Garfall, Alfred ;

Vogl, Dan T. ;

Xu, Xiaowei ;

Knight, Stella C. ;

Malietzis, George ;

Lee, Gui Han ;

Eruslanov, Evgeniy ;

Albelda, Steven M. ;

Wang, Xianwei ;

Mehta, Jawahar L. ;

Bewtra, Meenakshi ;

Rustgi, Anil ;

Hockstein, Neil ;

Witt, Robert ;

Masters, Gregory ;

Nam, Brian ;

Smirnov, Denis ;

Sepulveda, Manuel A. ;

Gabrilovich, Dmitry I. .

SCIENCE IMMUNOLOGY, 2016, 1 (02)

[23] Tumor cell cholesterol depletion and V-ATPase inhibition as an inhibitory mechanism to prevent cell migration and invasiveness in melanoma [J].

Costa, Gildeide Aparecida ;

de Souza, Savio Bastos ;

da Silva Teixeira, Layz Ribeiro ;

Okorokov, Lev A. ;

Veto Arnholdt, Andrea Cristina ;

Okorokova-Facanha, Anna L. ;

Facanha, Arnoldo Rocha .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2018, 1862 (03) :684-691

[24] Oxysterol receptors and their therapeutic applications in cancer conditions [J].

De Boussac, Hugues ;

Alioui, Anthony ;

Viennois, Emilie ;

Dufour, Julie ;

Trousson, Amalia ;

Vega, Aurelie ;

Guy, Laurent ;

Volle, David H. ;

Lobaccaro, Jean-Marc A. ;

Baron, Silvere .

EXPERT OPINION ON THERAPEUTIC TARGETS, 2013, 17 (09) :1029-1038

[25] Bile acids and colon cancer: Solving the puzzle with nuclear receptors [J].

Degirolamo, Chiara ;

Modica, Salvatore ;

Palasciano, Giuseppe ;

Moschetta, Antonio .

TRENDS IN MOLECULAR MEDICINE, 2011, 17 (10) :564-572

[26]

Ding X, 2019, AM J CANCER RES, V9, P219

[27] FSP1 is a glutathione-independent ferroptosis suppressor [J].

Doll, Sebastian ;

Freitas, Florencio Porto ;

Shah, Ron ;

Aldrovandi, Maceler ;

da Silva, Milene Costa ;

Ingold, Irina ;

Grocin, Andrea Goya ;

da Silva, Thamara Nishida Xavier ;

Panzilius, Elena ;

Scheel, Christina H. ;

Mourao, Andre ;

Buday, Katalin ;

Sato, Mami ;

Wanninger, Jonas ;

Vignane, Thibaut ;

Mohana, Vaishnavi ;

Rehberg, Markus ;

Flatley, Andrew ;

Schepers, Aloys ;

Kurz, Andreas ;

White, Daniel ;

Sauer, Markus ;

Sattler, Michael ;

Tate, Edward William ;

Schmitz, Werner ;

Schulze, Almut ;

O'Donnell, Valerie ;

Proneth, Bettina ;

Popowicz, Grzegorz M. ;

Pratt, Derek A. ;

Angeli, Jose Pedro Friedmann ;

Conrad, Marcus .

NATURE, 2019, 575 (7784) :693-+

[28] Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology [J].

Dumitru, Claudia A. ;

Moses, Katrin ;

Trellakis, Sokratis ;

Lang, Stephan ;

Brandau, Sven .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (08) :1155-1167

[29] Increased Cholesterol Biosynthesis Is a Key Characteristic of Breast Cancer Stem Cells Influencing Patient Outcome [J].

Ehmsen, Sidse ;

Pedersen, Martin H. ;

Wang, Guisong ;

Terp, Mikkel G. ;

Arslanagic, Amina ;

Hood, Brian L. ;

Conrads, Thomas P. ;

Leth-Larsen, Rikke ;

Ditzel, Henrik J. .

CELL REPORTS, 2019, 27 (13) :3927-+

[30] On the role of 25-hydroxycholesterol Synthesis by glioblastoma cell lines. Implications for chemotactic monocyte recruitment [J].

Eibinger, Gerald ;

Fauler, Guenter ;

Bernhart, Eva ;

Frank, Sasa ;

Hammer, Astrid ;

Wintersperger, Andrea ;

Eder, Hans ;

Heinemann, Akos ;

Mischel, Paul S. ;

Malle, Ernst ;

Sattler, Wolfgang .

EXPERIMENTAL CELL RESEARCH, 2013, 319 (12) :1828-1838

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