Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer

Hur, Hoon; Kim, Young‐Bae; Ham, In-Hye; Lee, Dakeun

doi:10.1002/jso.24043

Cited by 36 publications

(30 citation statements)

References 31 publications

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“…Bjornson et al., predicted that mitochondrial ACSS1 would be an important acetyl‐CoA provider that would be positively associated with hepatocellular carcinoma (HCC) prognosis . Another report indicates that the loss of ACSS2 could facilitate GCa progression , which is compatible with our results.…”

Section: Discussionsupporting

confidence: 91%

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Chang

Cheng

et al. 2018

Cancer Medicine

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Cholesterol affects cancer progression, and acetyl‐CoA is the primary cholesterogenesis substrate. The previous work has defined cholesterol bioflux via lipoprotein/receptor route is the gastric cancer (GCa) prognosis biosignature. The prognosis importance of acetyl‐CoA to cholesterogenesis (mevalonate pathway) in GCa is yet to be defined. Using Kaplan–Meier Plotter web‐based gene survival analyzer and The Cancer Genome Atlas (TCGA)‐database analyzed with DBdriver.v2 platform, we revealed acetyl‐CoA production and the mevalonate pathway are associated with GCa prognosis. We found mitochondrial‐derived acetyl‐CoA contributing enzymes (acyl‐coA synthetase super‐family 3; ACSS3) is the GCa progression confounder. Interestingly, it is not HMGCR (the committee enzyme of mevalonate pathway), but lower mevalonate pathway enzymes (e.g., MVK, LSS, DHCR14A1, SC4MOL, HSD17B7, SC5D) promote GCa patients 5‐years overall survival in a differential level. Advanced analyses found ACSS3 is prognosis biosignatures for multiple GCa disease conditions. This report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions, which implicates a targeting value for GCa therapy. While knockdown ACSS3 could suppress growth and invasion of GCa cells, of which even more impactful under starvation condition. This is the first report, surprisingly, revealed ACSS3 as important cancer prognosis biomarker. Targeting ACSS3 could be a novel therapeutic strategy for cancer, in this case, GCa.

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Section: Discussionsupporting

confidence: 91%

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Chang

Cheng

et al. 2018

Cancer Medicine

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“…(15,16) However, there are some controversies surrounding the effect of ACSS2 in tumors. Some scientists have recognized ACSS2 as a cancer-promoting factor, (13,14,32) whereas others have reported opposing results, in that the loss of ACSS2 expression predicts poor prognosis in patients, (34,35) especially in cancer of the digestive system. The theory of ACSS2 promoting tumors is mainly found in breast cancer and glioma, which emphasizes the role of ACSS2 in producing acetyl-CoA; the opposite opinion on ACSS2 in digestive system cancer is mainly from the IHC of clinical samples.…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of acetyl‐CoA synthase 2 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma

et al. 2017

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Metastasis is a serious risk that may occur during the treatment of hepatocellular carcinoma (HCC), preventing many patients from being surgical candidates and contributing to poor prognosis. Hypoxia has been proved an important factor of metastasis through the epithelial–mesenchymal transition (EMT) pathway. Acetyl‐CoA synthase 2 (ACSS2) provides an acetyl group for the acetylation of hypoxia‐inducible factor (HIF)‐2α, and this epigenetic modification affects the activity of HIF‐2α and the subsequent EMT process. Here, we showed that ACSS2 expression was negatively correlated with HCC malignancy. Knockdown of ACSS2 increased the invasion and migration ability of HCC cells and promoted EMT without increasing the total protein level of HIF‐2α, even in hypoxic conditions. The immunoprecipitation assay revealed downregulated acetylation levels of HIF‐2α after ACSS2 knockdown in hypoxic conditions, which resulted in enhanced HIF‐2α activity. Finally, decreased expression of ACSS2 was found to be related to advanced stage and poor overall survival and disease‐free survival rates in a cohort of patients with HCC. In conclusion, ACSS2 plays an important role in the acetylation process of HIF‐2α, which effectively modifies the activity of HIF‐2α under hypoxic conditions and greatly impacts on the prognosis of patients with HCC.

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“…We found a predicted gene annotated as ACS (accession no. TGGT1-266640) based on sequence homology with other characterized ACSs (35)(36)(37). The candidate protein was bearing typical domains for ACS, such as AMP binding (PF13193) and CoA binding (TIGR02188).…”

Section: Tgacs Is a Cytosolic Protein That Is Not Essential During Thmentioning

confidence: 99%

Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages

Dubois

Fernandes

Amiar

et al. 2018

Journal of Lipid Research

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Apicomplexan parasites are pathogens responsible for major human diseases such as toxoplasmosis caused by and malaria caused by spp. Throughout their intracellular division cycle, the parasites require vast and specific amounts of lipids to divide and survive. This demand for lipids relies on a fine balance between de novo synthesized lipids and scavenged lipids from the host. Acetyl-CoA is a major and central precursor for many metabolic pathways, especially for lipid biosynthesis. possesses a single cytosolic acetyl-CoA synthetase (ACS). Its role in the parasite lipid synthesis is unclear. Here, we generated an inducible ACS KO parasite line and confirmed the cytosolic localization of the protein. We conductedC-stable isotope labeling combined with mass spectrometry-based lipidomic analyses to unravel its putative role in the parasite lipid synthesis pathway. We show that its disruption has a minor effect on the global FA composition due to the metabolic changes induced to compensate for its loss. However, we could demonstrate that ACS is involved in providing acetyl-CoA for the essential fatty elongation pathway to generate FAs used for membrane biogenesis. This work provides novel metabolic insight to decipher the complex lipid synthesis in.

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Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer

Abstract: We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC.

Cited by 36 publications

References 31 publications

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Decreased expression of acetyl‐CoA synthase 2 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma

Toxoplasma gondii acetyl-CoA synthetase is involved in fatty acid elongation (of long fatty acid chains) during tachyzoite life stages

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