Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition

Zhu, Weiping; Zhao, Yiming; Zhou, Jiamin; Wang, Xin; Pan, Qi; Zhang, Ning; Wang, Longrong; Wang, Miao; Zhan, Di-Hua; Liu, Zeyang; He, Xinhong; Ma, Dongjie; Liu, Shuang

doi:10.1186/s13045-016-0361-3

Cited by 46 publications

(54 citation statements)

References 40 publications

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“…MAGL was highly expressed in ovarian and breast cancer tissues, and identified to contribute to tumorigenesis and metastasis through upregulation of free fatty acids (33). MAGL also promotes epithelialmesenchymal transition (EMT) and may serve as a gene expression signature for cancer stem cells (71,72).…”

Section: Monoacylglycerol Lipase (Magl)mentioning

confidence: 99%

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

Shen²,

et al. 2020

Front. Oncol.

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Ovarian cancer is one of the most malignant gynecological cancers around the world. In spite of multiple treatment options, the five-year survival rate is still very low. Several metabolism alterations are described as a hallmark in cancers, but alterations of lipid metabolism in ovarian cancer have been paid less attention. To explore new markers/targets for accurate diagnosis, prognosis, and therapeutic treatments based on metabolic enzyme inhibitors, here, we reviewed available literature and summarized several key metabolic enzymes in lipid metabolism of ovarian cancer. In this review, the rate limiting enzymes associated with fatty acid synthesis (FASN, ACC, ACLY, SCD), the lipid degradation related enzymes (MAGL, CPT, 5-LO, COX2), and the receptors related to lipid uptake (FABP4, CD36, LDLR), which promote the development of ovarian cancer, were analyzed and evaluated. We also focused on the review of application of current metabolic enzyme inhibitors for the treatment of ovarian cancer through which the potential therapeutic agents may be developed for ovarian cancer therapy.

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Section: Monoacylglycerol Lipase (Magl)mentioning

confidence: 99%

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

Shen²,

et al. 2020

Front. Oncol.

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“…While the role of ATGL in cancer is still debated due to incongruence between in vitro and in vivo evidence, the oncogenic role of MAGL, the third lipolytic enzyme, in cancer is well established 50 – 52 . Indeed, MAGL is highly expressed in many aggressive human cancers where it orchestrates lipid signalling-mediated tumorigenesis, migration and invasion, acting as a critical regulator of metastatization 52 – 54 .…”

Section: Metabolic Rewiring and Atgl Deregulation In Cancermentioning

confidence: 99%

Hints on ATGL implications in cancer: beyond bioenergetic clues

et al. 2018

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Among metabolic rearrangements occurring in cancer cells, lipid metabolism alteration has become a hallmark, aimed at sustaining accelerated proliferation. In particular, fatty acids (FAs) are dramatically required by cancer cells as signalling molecules and membrane building blocks, beyond bioenergetics. Along with de novo biosynthesis, free FAs derive from dietary sources or from intracellular lipid droplets, which represent the storage of triacylglycerols (TAGs). Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis, catalysing the first step of intracellular TAGs hydrolysis in several tissues. However, the roles of ATGL in cancer are still neglected though a putative tumour suppressor function of ATGL has been envisaged, as its expression is frequently reduced in different human cancers (e.g., lung, muscle, and pancreas). In this review, we will introduce lipid metabolism focusing on ATGL functions and regulation in normal cell physiology providing also speculative perspectives on potential non-energetic functions of ATGL in cancer. In particular, we will discuss how ATGL is implicated, mainly through the peroxisome proliferator-activated receptor-α (PPAR-α) signalling, in inflammation, redox homoeostasis and autophagy, which are well-known processes deregulated during cancer formation and/or progression.

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“…MAGL is a crucial lipolytic enzyme and an important regulator of tumor progression. It can promote hepatocellular carcinoma progression and was recently suggested as a potential therapeutic target and as a biomarker for prognosis in patients with HCC (Zhu et al, 2016 ). Expression of HSL is decreased in NAFLD compared with normal liver (Kohjima et al, 2007 ), which was also observed in our simulation results.…”

Section: Discussionmentioning

confidence: 99%

LiverSex Computational Model: Sexual Aspects in Hepatic Metabolism and Abnormalities

et al. 2018

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The liver is to date the best example of a sexually dimorphic non-reproductive organ. Over 1,000 genes are differentially expressed between sexes indicating that female and male livers are two metabolically distinct organs. The spectrum of liver diseases is broad and is usually prevalent in one or the other sex, with different contributing genetic and environmental factors. It is thus difficult to predict individual's disease outcomes and treatment options. Systems approaches including mathematical modeling can aid importantly in understanding the multifactorial liver disease etiology leading toward tailored diagnostics, prognostics and therapy. The currently established computational models of hepatic metabolism that have proven to be essential for understanding of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are limited to the description of gender-independent response or reflect solely the response of the males. Herein we present LiverSex, the first sex-based multi-tissue and multi-level liver metabolic computational model. The model was constructed based on in silico liver model SteatoNet and the object-oriented modeling. The crucial factor in adaptation of liver metabolism to the sex is the inclusion of estrogen and androgen receptor responses to respective hormones and the link to sex-differences in growth hormone release. The model was extensively validated on literature data and experimental data obtained from wild type C57BL/6 mice fed with regular chow and western diet. These experimental results show extensive sex-dependent changes and could not be reproduced in silico with the uniform model SteatoNet. LiverSex represents the first large-scale liver metabolic model, which allows a detailed insight into the sex-dependent complex liver pathologies, and how the genetic and environmental factors interact with the sex in disease appearance and progression. We used the model to identify the most important sex-dependent metabolic pathways, which are involved in accumulation of triglycerides representing initial steps of NAFLD. We identified PGC1A, PPARα, FXR, and LXR as regulatory factors that could become important in sex-dependent personalized treatment of NAFLD.

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Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF-κB-mediated epithelial-mesenchymal transition

Cited by 46 publications

References 40 publications

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer

Hints on ATGL implications in cancer: beyond bioenergetic clues

LiverSex Computational Model: Sexual Aspects in Hepatic Metabolism and Abnormalities

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