Lipid Metabolic Reprogramming and Metabolic Stress in Liver Cancer

XU Zhe, YUAN Ke-fei

Abstract

Recent studies have shown that tumor microenvironment plays an important regulatory role in the growth and metastasis of liver cancer. Metabolic reprogramming represents a series of adaptive metabolic alterations that liver cancer cells undertake when they are under metabolic stress caused by glucose deficiency and hypoxia microenvironment, and lipid reprogramming is an important part of it. Previous studies have revealed a variety of lipid types with altered metabolic patterns in liver cancer cells, and have, to a certain extent, investigated the biological functions and regulatory mechanisms of these lipid metabolic reprogramming processes. However, there are still many lipid metabolic reprogramming processes that have not received thorough investigation, and little is known about their roles and mechanisms in the pathogenesis and development of liver cancer. In addition, how to accomplish the goal of treating liver cancer by targeting key regulatory factors in lipid metabolic reprogramming still remains a major challenge in translational medical research. This paper introduced the sources of lipids and the main functions and driving factors of lipid metabolic reprogramming in liver cancer cells, attempting to provide a theoretical basis and potential therapeutic targets for the treatment of liver cancer through regulating or restricting lipid metabolic reprogramming.

 

Keywords: Liver cancer, Tumor microenvironment, Lipid metabolism, Metabolic reprogramming

 

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KLAJER E， GARNIER L， GOUJON M， et al. Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review. Semin Onco，2020，47(2/3): 103–116.

LEONARDI G C， CANDIDO S， CERVELLO M， et al. The tumor microenvironment in hepatocellular carcinoma (Review). Int J Oncol， 2012，40(6): 1733–1747.

LI S， LIU R， PAN Q， et al. De novo lipogenesis is elicited dramatically in human hepatocellular carcinoma especially in hepatitis C virus‐induced hepatocellular carcinoma. Med Comm，2020，1(2): 178–187.

GAO X， LIN S H， REN F， et al. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat Commun， 2016，7(1): 11960.

WANG X， HASSAN W， JABEEN Q， et al. Interdependent and independent multidimensional role of tumor microenvironment on hepatocellular carcinoma. Cytokine，2018，103: 150–159.

HU B， LIN J Z， YANG X B， et al. Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review. Cell Prolif，2020，53(3): e12772[2020-12-12]. https://doi.org/10. 1111/cpr.12772.

IPSEN D H， LYKKESFELDT J， TVEDEN-NYBORG P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci，2018，75(18): 3313–3327.

BECHMANN L P， HANNIVOORT R A， GERKEN G， et al. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol，2012，56(4): 952–964.

CASSIM S， RAYMOND V A， DEHBIDI-ASSADZADEH L， et al. Metabolic reprogramming enables hepatocarcinoma cells to efficiently adapt and survive to a nutrient-restricted microenvironment. Cell Cycle， 2018，17(7): 903–916.

LI Y， CAI W， YI Q， et al. Lipid droplets may lay a spacial foundation for vasculogenic mimicry formation in hepatocellular carcinoma. Med Hypotheses，2014，83(1): 56–59.

HEIDEN M G V， CANTLEY L C， THOMPSON C B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science， 2009，324(5930): 1029–1033.

PIKE L S， SMIFT A L， CROTEAU N J， et al. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta，2011，1807(6): 726–734.

WANG H C. Fatty acid synthase and the lipogenic phenotype in WSSV-infected shrimp. Fish and Shellfish Immunology，2016，53: 61–61.

LIN H P， CHENG Z L， HE R Y， et al. Destabilization of fatty acid synthase by acetylation inhibits de novo lipogenesis and tumor cell growth. Cancer Res，2016，76(23): 6924–6936.

MACH N， JACOBS A， KRUIJT L， et al. Alteration of gene expression in mammary gland tissue of dairy cows in response to dietary unsaturated fatty acids. Animal，2011，5(8): 1217–1230.

CUI M， WANG Y， SUN B， et al. MiR-205 modulates abnormal lipid metabolism of hepatoma cells via targeting acyl-CoA synthetase long-chain family member 1 (ACSL1) mRNA. Biochem Biophys Res Commun，2014，444(2): 270–275.

LLIOPOULOS D， DROSATOS K， HLYAMA Y， et al. Micro RNA-370 controls the expression of micro RNA-122 and Cpt1α and affects lipid metabolism. Lipid Res，2010，51(6): 1513–1523.

HICKS J A， TRAKOOLJUL N， LIU H C. Discovery of chocken micro RNAs associated with lipogenesis and cell proliferation. Physiol Genomics，2010，41(2): 185–193.

ZHU D Q， LOU Y F， HE Z G， et al. Nucleotidyl transferase TUT1 inhibits lipogenesis in osteosarcoma cells through regulation of microRNA-24 and microRNA-29a. Tumor Biol，2014，35(12): 11829–11835.

MENENDEZ J A， LUPU R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin Ther Targets，2017，21(11): 1001–1016.


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