The Role of Lipids in Hepatocellular Carcinoma

Hayes, C. Nelson; Zhang, Peiyi; Chayama, Kazuaki

doi:10.15586/hepatocellularcarcinoma.2019.ch5

Cited by 10 publications

(2 citation statements)

References 104 publications

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“…Liver lipidome has been examined in tissue and serum samples of patients with HCC or non‐alcoholic fatty liver disease (NAFLD), a chronic liver disease and the fastest‐growing cause of HCC [ 73 , 74 , 75 , 76 , 77 ]. Due to the liver's essential roles in lipid metabolism, altered lipid metabolism in hepatic cells contributes to the progression of HCC, by providing the neoplastic cells with energy and supporting the growth of HCC lesions in humans [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

“…Due to the liver's essential roles in lipid metabolism, altered lipid metabolism in hepatic cells contributes to the progression of HCC, by providing the neoplastic cells with energy and supporting the growth of HCC lesions in humans [ 78 ]. The changes in lipid metabolism and the levels of different lipids have been associated with the severity of HCC [ 75 ]. However, these studies are mainly based on the data obtained from whole tissues or serum, presumably leading to heterogeneity in the role of lipids in HCC.…”

Section: Discussionmentioning

confidence: 99%

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Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Azbazdar,

Demirci,

Heger

et al. 2023

Molecular Oncology

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Hepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/β‐catenin signaling. Nevertheless, how membrane lipid composition is altered in HCC cells with abnormal Wnt signaling remains elusive. Here, by exploiting comprehensive lipidome profiling, we unravel the membrane lipid composition of six different HCC cell lines with mutations in components of Wnt/β‐catenin signaling, leading to differences in their endogenous signaling activity. Among the differentially regulated lipids are diacylglycerol (DAG) and ceramide, which were downregulated at the membrane of HCC cells after Wnt3a treatment. DAG and ceramide enhanced Wnt/β‐catenin signaling by inducing caveolin‐mediated endocytosis of the canonical Wnt‐receptor complex, while their depletion suppressed the signaling activity along with a reduction of caveolin‐mediated endocytosis in SNU475 and HepG2 cells. Moreover, depletion of DAG and ceramide significantly impeded the proliferation, tumor growth, and in vivo migration capacity of SNU475 and HepG2 cells. This study, by pioneering plasma membrane lipidome profiling in HCC cells, exhibits the remarkable potential of lipids to correct dysregulated signaling pathways in cancer and stop abnormal tumor growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Azbazdar,

Demirci,

Heger

et al. 2023

Molecular Oncology

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Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

et al. 2020

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Arrb2 causes hepatic lipid metabolism disorder via AMPK pathway based on metabolomics in alcoholic fatty liver

Yin

Yang

et al. 2021

Clinical Science

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Background & Aims: Alcoholic fatty liver (AFL) is an early form of alcoholic liver disease (ALD) that usually manifests as lipid synthesis abnormalities in hepatocytes. Arrb2 is involved in multiple biological processes. This study aimed to explore the role of Arrb2 in the regulation of lipid metabolism in AFL and the underlying mechanism and identify potential targets for the treatment of AFL. Methods: The expression of Arrb2 was detected in liver tissues obtained from AFL patients and Gao-binge AFL model mice. In addition, we specifically knocked down Arrb2 in AFL mouse liver in vivo and used Arrb2-siRNA or pEX3-Arrb2 to silence or overexpress Arrb2 in AML-12 cells in vitro to explore the functional role and underlying regulatory mechanism of Arrb2 in AFL. Finally, we investigated whether Arrb2 could cause changes in hepatic lipid metabolites, thereby leading to dysregulation of lipid metabolism based on liquid chromatography-mass spectrometry (LC-MS) analysis. Results: Arrb2 was upregulated in the livers of AFL patients and AFL mice. The in vivo and in vitro results confirmed that Arrb2 could induce lipid accumulation and metabolism disorders. Mechanistically, Arrb2 induced hepatic metabolism disorder via AMP-activated protein kinase (AMPK) pathway. The results of LC-MS analysis revealed that hepatic lipid metabolites with the most significant differences were primary bile acids. Conclusions: Arrb2 induces hepatic lipid metabolism disorders via AMPK pathway in AFL. On one hand, Arrb2 increases fatty acid synthesis. On the other hand, Arrb2 could increase the cholesterol synthesis, thereby leading to the upregulation of primary bile acid levels.

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The Role of Lipids in Hepatocellular Carcinoma

Cited by 10 publications

References 104 publications

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Dysregulated lipid metabolism in hepatocellular carcinoma cancer stem cells

Arrb2 causes hepatic lipid metabolism disorder via AMPK pathway based on metabolomics in alcoholic fatty liver

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