Targeting Sterol-O-acyltransferase 1 to Disrupt Cholesterol Metabolism for Cancer Therapy

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Jul 6

PMID 37409263

Authors

Teng Tu

Hongying Zhang

Huanji Xu

Affiliations

Soon will be listed here.

Abstract

Cholesterol esterification is often dysregulated in cancer. Sterol O-acyl-transferase 1 (SOAT1) plays an important role in maintaining cellular cholesterol homeostasis by catalyzing the formation of cholesterol esters from cholesterol and long-chain fatty acids in cells. Many studies have implicated that SOAT1 plays a vital role in cancer initiation and progression and is an attractive target for novel anticancer therapy. In this review, we provide an overview of the mechanism and regulation of SOAT1 in cancer and summarize the updates of anticancer therapy targeting SOAT1.

Citing Articles

Targeting ACAT1 in cancer: from threat to treatment.

Sun T, Xiao X Front Oncol. 2024; 14:1395192.

PMID: 38720812 PMC: 11076747. DOI: 10.3389/fonc.2024.1395192.

References

van Weverwijk A, de Visser K . Mechanisms driving the immunoregulatory function of cancer cells. Nat Rev Cancer. 2023; 23(4):193-215. DOI: 10.1038/s41568-022-00544-4. View

Espinosa G, Lopez-Montero I, Monroy F, Langevin D . Shear rheology of lipid monolayers and insights on membrane fluidity. Proc Natl Acad Sci U S A. 2011; 108(15):6008-13. PMC: 3076832. DOI: 10.1073/pnas.1018572108. View

Lei L, Xiong Y, Chen J, Yang J, Wang Y, Yang X . TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation. J Lipid Res. 2009; 50(6):1057-67. PMC: 2681388. DOI: 10.1194/jlr.M800484-JLR200. View

Goldstein J, DeBose-Boyd R, Brown M . Protein sensors for membrane sterols. Cell. 2006; 124(1):35-46. DOI: 10.1016/j.cell.2005.12.022. View

Wei L, Lu X, Weng S, Zhu S, Chen Y . Cholesteryl Ester Promotes Mammary Tumor Growth in MMTV-PyMT Mice and Activates Akt-mTOR Pathway in Tumor Cells. Biomolecules. 2021; 11(6). PMC: 8228430. DOI: 10.3390/biom11060853. View

Lohr M, Hartig W, Schulze A, Kroiss M, Sbiera S, Lapa C . SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?. Int J Mol Sci. 2022; 23(7). PMC: 8998855. DOI: 10.3390/ijms23073726. View

Kou Y, Geng F, Guo D . Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage. Biomedicines. 2022; 10(8). PMC: 9405736. DOI: 10.3390/biomedicines10081943. View

Luo J, Yang H, Song B . Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2019; 21(4):225-245. DOI: 10.1038/s41580-019-0190-7. View

Lee H, Sliskovic D, Picard J, Roth B, Wierenga W, Hicks J . Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. CI-1011: an acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets. J Med Chem. 1996; 39(26):5031-4. DOI: 10.1021/jm960674d. View

10.

Buhman K, Accad M, Novak S, Choi R, Wong J, Hamilton R . Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med. 2000; 6(12):1341-7. DOI: 10.1038/82153. View

11.

Zhong N, Nong X, Diao J, Yang G . piRNA-6426 increases DNMT3B-mediated SOAT1 methylation and improves heart failure. Aging (Albany NY). 2022; 14(6):2678-2694. PMC: 9004576. DOI: 10.18632/aging.203965. View

12.

Moon S, Huang C, Houlihan S, Regunath K, Freed-Pastor W, Morris 4th J . p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression. Cell. 2018; 176(3):564-580.e19. PMC: 6483089. DOI: 10.1016/j.cell.2018.11.011. View

13.

INSULL Jr W, Koren M, Davignon J, Sprecher D, Schrott H, Keilson L . Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia. Atherosclerosis. 2001; 157(1):137-44. DOI: 10.1016/s0021-9150(00)00615-8. View

14.

Chen Y, Yang X, Chen Y, Chen G, Winkler C, An P . Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma. BMC Cancer. 2021; 21(1):615. PMC: 8152151. DOI: 10.1186/s12885-021-08245-1. View

15.

Kuldeep S, Soni S, Srivastava A, Mishra A, Sharma L, Mandal C . Dysregulated cholesterol regulatory genes as a diagnostic biomarker for cancer. J Gene Med. 2023; 25(4):e3475. DOI: 10.1002/jgm.3475. View

16.

Wang X, Luo L, Huang T, Feng L . SOAT1 is a new prognostic factor of colorectal cancer. Ir J Med Sci. 2021; 191(4):1549-1554. DOI: 10.1007/s11845-021-02746-5. View

17.

Guan C, Niu Y, Chen S, Kang Y, Wu J, Nishi K . Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. Nat Commun. 2020; 11(1):2478. PMC: 7234994. DOI: 10.1038/s41467-020-16288-4. View

18.

Guo X, Zhou S, Yang Z, Li Z, Hu W, Dai L . Comprehensive Analysis of as a Prognostic Biomarker and Its Association With Immune Infiltration in Glioma. Front Oncol. 2022; 12:896433. PMC: 9133349. DOI: 10.3389/fonc.2022.896433. View

19.

Yue S, Li J, Lee S, Lee H, Shao T, Song B . Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014; 19(3):393-406. PMC: 3969850. DOI: 10.1016/j.cmet.2014.01.019. View

20.

Oni T, Biffi G, Baker L, Hao Y, Tonelli C, Somerville T . SOAT1 promotes mevalonate pathway dependency in pancreatic cancer. J Exp Med. 2020; 217(9). PMC: 7478739. DOI: 10.1084/jem.20192389. View