Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma

Jung, Woon Yong; Kim, Young Hye; Ryu, Young Joon; Kim, Baek Hui; Shin, Bong Kyung; Kim, Aeree; Kim, Han Kyeom

doi:10.1016/j.prp.2013.02.008

Cited by 15 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that different types of lung cancer may possess unique metabolic networks. Although previous studies have demonstrated associations between a single enzyme and a specific tumor type, including the association between ACSL3, ACOT8 and liver cancer (25,26), very long-chain ACS-3 (ACSVL3) and lung cancer (27), and ACOT8 and metastatic lung adenocarcinoma (9), the associations between types of tumor and the enzyme network of acyl-CoA and acyl-CoA esters remain unclear. To systematically determine the potential roles of all ACS and ACOT enzymes in lung adenocarcinoma, the gene expression values from six different microarray datasets were analyzed using five different platforms.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with healthy individuals, patients with lung adenocarcinoma possess a significantly higher level of fatty acids (including arachidonic, palmitic, linoleic and oleic acid) in their plasma (7,8). In addition, overexpression of ACOT8 is associated with metastasis in lung adenocarcinoma (9). However, the cellular functions and the regulatory mechanisms of the majority of ACOT and ACS enzymes in lung adenocarcinoma remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

Abstract. The metabolites of fatty acyl-Coenzyme A (CoA) and metabolic enzymes contribute to lipid biosynthesis, signal transduction, and gene transcription. Previous studies have indicated that elevated concentrations of specific free fatty acids in the plasma and overexpression of specific fatty acyl-CoA metabolic enzymes are observed in patients with lung adenocarcinoma. However, there are >30 enzymes in this metabolic network and have been fully investigated. In the present study, the expression levels of enzymes in the acyl-CoA synthetase (ACS) and acyl-CoA thioesterase (ACOT) families were analyzed from six microarray expression datasets that were collected from Gene Expression Omnibus. Compared with adjacent non-tumor lung tissue, lung adenocarcinoma tissue exhibited significantly higher ACOT11 and ACOT13 expression. Kaplan-Meier plotter database analysis demonstrated that high levels of ACOT11 and ACOT13 were associated with a worse overall survival rate. The proliferation of the lung adenocarcinoma cell lines CL1-0 and CL1-5 was inhibited when ACOT11 and ACOT13 were downregulated by short hairpin RNA. Although ACOT11 and ACOT13 knockdown did not significantly affect the total amount of intracellular and medium-free fatty acids, ACOT11 and ACOT13 knockdown-mediated growth inhibition was rescued by the addition of fatty acids. In conclusion, ACOT11 and ACOT13 were upregulated in clinical specimens of lung adenocarcinoma, which may contribute to increased cell proliferation through the increased availability of fatty acids. The metabolites of the two enzymes may be critical for development of lung adenocarcinoma. IntroductionMetabolites are currently considered targets for cancer treatments, particularly amino acids and glucose (1). Fatty acyl-Coenzyme A (CoA) esters are essential components in lipid metabolism and are regulators of multiple cellular functions (2). Enzymes of the acyl-CoA synthetase (ACS) family, including the ACS long-chain, ACS medium-chain, ACS short-chain and ACS bubblegum families, ligate different lengths of fatty acid with CoA. Fatty acyl-CoA esters are hydrolyzed into free fatty acids and CoA by enzymes of the acyl-CoA thioesterase (ACOT) family (3,4). There are >15 ACOT enzymes and 20 ACS enzymes in humans, and these enzymes exhibit different tissue distribution, subcellular location and substrate specificity (3,4).Lung cancer is a leading cause of cancer-associated mortality and is the second most commonly diagnosed cancer (5). The majority (~85-90%) of diagnosed cases of lung cancer are diagnosed as non-small cell lung cancer (NSCLC) and adenocarcinoma is the most common subtype of NSCLC (6). Compared with healthy individuals, patients with lung adenocarcinoma possess a significantly higher level of fatty acids (including arachidonic, palmitic, linoleic and oleic acid) in their plasma (7,8). In addition, overexpression of ACOT8 is associated with metastasis in lung adenocarcinoma (9). However, the cellular functions and the regulatory mechanisms of the majority of ACOT and ACS e...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

show abstract

“…ACOT8 expression is increased in human hepatocellular carcinoma, and cell culture studies suggest a pathogenic role for the enzyme [47]. In lung adenocarcinoma, ACOT8 is upregulated in lymph node metastases and is associated with a poorer prognosis [48]. Whether ACOT8 contributes to tumorigenesis via its enzymatic activity or its capacity to induce peroxisomal proliferation is unclear.…”

Section: Type II Acotsmentioning

confidence: 99%

Deactivating Fatty Acids: Acyl-CoA Thioesterase-Mediated Control of Lipid Metabolism

Tillander

Alexson

Cohen

2017

Trends in Endocrinology & Metabolism

141

147

View full text Add to dashboard Cite

The cellular uptake of free fatty acids (FFA) is followed by esterification to coenzyme A (CoA), generating fatty acyl-CoAs that are substrates for oxidation or incorporation into complex lipids. Acyl-CoA thioesterases constitute a family of enzymes that hydrolyze fatty acyl-CoAs to form FFA and CoA. Although biochemically and biophysically well characterized, the metabolic functions of these enzymes remain incompletely understood. Existing evidence suggests regulatory roles in controlling rates of peroxisomal and mitochondrial fatty acyl-CoA oxidation, as well as in the subcellular trafficking of fatty acids. Emerging data implicate acyl-CoA thioesterases in the pathogenesis of metabolic diseases, suggesting that better understanding their pathobiology could reveal unique targets in the management of obesity, diabetes and non-alcoholic fatty liver disease.

show abstract

“…Recent studies have demonstrated the critical role of these enzymes in lung cancer. An increased risk of lymph node metastasis in lung adenocarcinoma is associated with high ACOT8 expression (20). Our previous study revealed that high expression of ACOT11 and ACOT13 in patients with lung adenocarcinoma was associated with cell proliferation and poor prognosis (21).…”

Section: Introductionmentioning

confidence: 94%

Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Liu

Yeh

Chou³

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) is an organelle involved in various physiological processes such as lipid metabolism, protein synthesis and folding, and cellular calcium storage. In a physiological tumor microenvironment, hypoxia, nutrient deprivation, and calcium dysregulation cause accumulation of unfolded and misfolded proteins. Such accumulation induces ER stress and unfolded protein responses (UPRs). Increased UPR signaling pathways are associated with multiple types of cancer. The influence of ER stress on acyl‑CoA metabolic enzymes is not well understood. Evaluation of PRECOG and Kaplan‑Meier plotter databases in the present study suggested that high expression of acyl‑CoA thioesterase (ACOT)7, ACOT11, ACOT13, soluble carrier family 27 member A4 (SLC27A4) and SLC27A5 was associated with poor clinical outcomes. In addition, expression levels of ACOT7, ACOT11, SLC27A4 and SLC27A5 were not altered after induction of ER stress. By contrast, expression of some enzymes was decreased, such as those of long‑chain acyl‑CoA synthetase (ACSL)3, ACSL4 and SLC27A2. Fatty acid uptake capacity was suppressed in lung cancer cell lines A549 and CL1‑0 after thapsigargin treatment but intracellular reactive oxygen species levels were not suppressed. Gene enrichment and regulatory element analysis were performed; the results provided potential targets for further investigation. On the whole, our findings demonstrate the potential regulatory mechanism of high‑expression of acyl‑CoA metabolic enzymes, the biological effects of decreased enzyme expression levels, possible regulatory elements, and the interaction network involved in responses to ER stress in lung cancer.

show abstract

Acyl-CoA thioesterase 8 is a specific protein related to nodal metastasis and prognosis of lung adenocarcinoma

Cited by 15 publications

References 31 publications

Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma

Overexpression and proliferation dependence of acyl-CoA thioesterase 11 and 13 in lung adenocarcinoma

Deactivating Fatty Acids: Acyl-CoA Thioesterase-Mediated Control of Lipid Metabolism

Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Contact Info

Product

Resources

About