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Semin Liver Dis 2022; 42(01): 077-086
DOI: 10.1055/s-0041-1731709
Review Article

Role of Lipogenesis Rewiring in Hepatocellular Carcinoma

Yi Zhou
1   Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
2   Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
,
Junyan Tao
3   Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
4   Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
,
Diego F. Calvisi
5   Institute of Pathology, University of Regensburg, Germany
,
Xin Chen
2   Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California
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Abstract

Metabolic rewiring is one of the hallmarks of cancer. Altered de novo lipogenesis is one of the pivotal metabolic events deregulated in cancers. Sterol regulatory element-binding transcription factor 1 (SREBP1) controls the transcription of major enzymes involved in de novo lipogenesis, including ACLY, ACACA, FASN, and SCD. Studies have shown the increased de novo lipogenesis in human hepatocellular carcinoma (HCC) samples. Multiple mechanisms, such as activation of the AKT/mechanistic target of rapamycin (mTOR) pathway, lead to high SREBP1 induction and the coordinated enhanced expression of ACLY, ACACA, FASN, and SCD genes. Subsequent functional analyses have unraveled these enzymes' critical role(s) and the related de novo lipogenesis in hepatocarcinogenesis. Importantly, targeting these molecules might be a promising strategy for HCC treatment. This paper comprehensively summarizes de novo lipogenesis rewiring in HCC and how this pathway might be therapeutically targeted.

Keywords

hepatocellular carcinoma - lipogenesis - targeted therapy

Financial Support

This study is supported by NIH grants R01CA190606 and R01CA239251 to XC; P30DK026743 to UCSF Liver Center.




Publication History

Article published online:
26 July 2021

© 2021. Thieme. All rights reserved.

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