ATP citrate lyase: A central metabolic enzyme in cancer

Icard, Philippe; Wu, Zherui; Fournel, Ludovic; Coquerel, Antoine; Lincet, Hubert; Alifano, Marco

doi:10.1016/j.canlet.2019.12.010

Cited by 157 publications

(133 citation statements)

References 105 publications

(179 reference statements)

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“…of ACLY can reduce its expression, thus protecting against gastric cancer cell progression (Guo et al, 2016;Icard et al, 2020). In addition, ACLY can be downregulated by miR-133b via PPARg (Cheng et al, 2017) and lncRNA FLJ22763 (Zhang et al, 2019) in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…ACLY is the integral enzyme responsible for the formation of cytosolic acetyl-CoA, and high expression of ACLY was shown to be associated with a poor prognosis ( Qian et al, 2015 ). Citrate and inhibitors of ACLY can reduce its expression, thus protecting against gastric cancer cell progression ( Guo et al, 2016 ; Icard et al, 2020 ). In addition, ACLY can be downregulated by miR-133b via PPARγ ( Cheng et al, 2017 ) and lncRNA FLJ22763 ( Zhang et al, 2019 ) in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

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Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

Zheng

Wang

Zheng³

et al. 2020

Front. Pharmacol.

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Weighted correlation network analysis (WGCNA) is a statistical method that has been widely used in recent years to explore gene co-expression modules. Competing endogenous RNA (ceRNA) is commonly involved in the cancer gene expression regulation mechanism. Some ceRNA networks are recognized in gastric cancer; however, the prognosisassociated ceRNA network has not been fully identified using WGCNA. We performed WGCNA using datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) to identify cancer-associated modules. The criteria of differentially expressed RNAs between normal stomach samples and gastric cancer samples were set at the false discovery rate (FDR) < 0.01 and |fold change (FC)| > 1.3. The ceRNA relationships obtained from the RNAinter database were examined by both the Pearson correlation test and hypergeometric test to confirm the mRNA-lncRNA regulation. Overlapped genes were recognized at the intersections of genes predicted by ceRNA relationships, differentially expressed genes, and genes in cancer-specific modules. These were then used for univariate and multivariate Cox analyses to construct a risk score model. The ceRNA network was constructed based on the genes in this model. WGCNAuncovered genes in the green and turquoise modules are those most associated with gastric cancer. Eighty differentially expressed genes were observed to have potential prognostic value, which led to the identification of 12 prognosis-related mRNAs (KIF15, FEN1, ZFP69B, SP6, SPARC, TTF2, MSI2, KYNU, ACLY, KIF21B, SLC12A7, and ZNF823) to construct a risk score model. The risk genes were validated using the GSE62254 and GSE84433 datasets, with 0.82 as the universal cutoff value. 12 genes, 12 lncRNAs, and 35 miRNAs were used to build a ceRNA network with 86 dysregulated lncRNA-mRNA ceRNA pairs. Finally, we developed a 12-gene signature from both prognosis-related and tumorspecific genes, and then constructed a ceRNA network in gastric cancer. Our findings may provide novel insights into the treatment of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

Zheng

Wang

Zheng³

et al. 2020

Front. Pharmacol.

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“…Similar results have been observed in EGFRvIII human GBM cells. ACLY, a key cytoplasmic enzyme catalyzing citric acid to acetyl‐CoA, is overexpressed in GBM, colorectal cancer, breast cancer, nonsmall cell lung cancer, and HCC 224‐226 . The ACLY inhibitor SB‐204990 has been shown to inhibit the proliferation of lung cancer cells in vivo and in vitro 227 .…”

Section: Therapeutic Strategies Targeting Lipid Metabolism Reprogrammmentioning

confidence: 99%

Lipid metabolism in cancer progression and therapeutic strategies

Zou

Shen

et al. 2020

MedComm

156

113

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Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression. The rewiring of lipid metabolism in cancer has been linked to the activation of oncogenic signaling pathways and cross talk with the tumor microenvironment. The resulting activity favors the survival and proliferation of tumor cells in the harsh conditions within the tumor. Lipid metabolism also plays a vital role in tumor immunogenicity via effects on the function of the noncancer cells within the tumor microenvironment, especially immune‐associated cells. Targeting altered lipid metabolism pathways has shown potential as a promising anticancer therapy. Here, we review recent evidence implicating the contribution of lipid metabolic reprogramming in cancer to cancer progression, and discuss the molecular mechanisms underlying lipid metabolism rewiring in cancer, and potential therapeutic strategies directed toward lipid metabolism in cancer. This review sheds new light to fully understanding of the role of lipid metabolic reprogramming in the context of cancer and provides valuable clues on therapeutic strategies targeting lipid metabolism in cancer.

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“…Since ACLY is responsible for converting citrate into acetyl-CoA and oxaloacetate during the process of FA biosynthesis [12], we then further investigated whether NONO affected oxaloacetate production in DEN-stimulated HCC cells. As shown in Fig.…”

Section: Nono Promotes Hcc Progression By Interacting With Acly Mrna mentioning

confidence: 99%

“…Generally, cancer cells use cytoplasmic acetyl-CoA as substrate for FA synthesis. Citrate, produced during citric acid cycle in mitochondria, is transported from mitochondria into cytoplasm, and then converted by ATP-citrate lyase (ACLY) into acetyl-CoA and oxaloacetate [12]. In the cytoplasm, acetyl-CoA is converted by acetyl-CoA carboxylase (ACC) to malonyl-CoA.…”

Section: Introductionmentioning

confidence: 99%

NONO promotes hepatocellular carcinoma progression by enhancing fatty acids biosynthesis through interacting with ACLY mRNA

et al. 2020

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Background: Dysregulation of fatty acid (FA) metabolism is involved in hepatocellular carcinoma (HCC) development. Non-POU domain-containing octamer binding protein (NONO), known as the component of nuclear paraspeckles, has recently been found to promote HCC progression. In this study, we investigated the functions of NONO in regulating de novo FA synthesis and its underling mechanism during HCC development. Methods: The roles of NONO in HCC development by applying gene function loss analysis in HCC cells were detected by quantitative real-time polymerase chain reaction, cell proliferation, and cell invasion assays. The underlying mechanism of NONO in HCC development was examined by western blotting, subcellular fractionation, RNAbinding protein immunoprecipitation-sequencing, chromatin immunoprecipitation, co-immunoprecipitation and mass spectrometry. The effect of NONO on tumorigenesis in vivo was performed with a subcutaneous xenograft mouse model of HCC. Results: NONO promotes HCC progression by interacting with and increasing ATP-citrate lyase (ACLY) mRNA to enhance FA biosynthesis. Furthermore, NONO promotes ACLY expression through enhancing nuclear ACLY mRNA stability in Diethylnitrosamine-stimulated HCC cells, not related to nuclear paraspeckles. Moreover, we find that NONO/ SFPQ (Splicing factor proline and glutamine rich) heterodimer is essential for NONO interacting with ACLY mRNA in DEN stimulated HCC cells. In addition, NONO, Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and ACLY expressions contribute HCC development in mice and are related to poor survival. Conclusion: NONO promotes HCC progression by enhancing FA biosynthesis through interacting with ACLY mRNA and provide a novel potential target for HCC therapy.

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ATP citrate lyase: A central metabolic enzyme in cancer

Cited by 157 publications

References 105 publications

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

Construction and Analysis of the Tumor-Specific mRNA–miRNA–lncRNA Network in Gastric Cancer

Lipid metabolism in cancer progression and therapeutic strategies

NONO promotes hepatocellular carcinoma progression by enhancing fatty acids biosynthesis through interacting with ACLY mRNA

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