The metabolic fate of acetate in cancer

Schug, Zachary T.; Voorde, Johan Vande; Gottlieb, Eyal

doi:10.1038/nrc.2016.87

Cited by 254 publications

(247 citation statements)

References 115 publications

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“…Many previous experiments have shown that ACSS2 is overexpressed in a large proportion of human cancers, including hepatocellular carcinoma, glioblastoma, breast cancer and prostate cancer [24]. Our results provide further evidence that ACSS2 expression is also abnormally upregulated in RCC cells.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andsupporting

confidence: 74%

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Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Guo

Gui

2018

Cell Physiol Biochem

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Background/Aims: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression was achieved by RNA interference, which was confirmed by qRT-PCR and Western blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a flow cytometry analysis, respectively. Cell migration and invasion were determined by the scratch and transwell assays. Following the knockdown of ACSS2 expression, the expression of the autophagy-related factor LAMP1 was measured by qRT-PCR and Western blotting. Results: Compared to adjacent tissues, ACSS2 expression was upregulated in RCC cancer tissues and positively correlated with metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell migration and invasion. ACSS2 was determined to promote the expression of LAMP1, which can also promote cell migration. This pathway may be considered a potential mechanism through which ACSS2 participates in RCC development. Conclusion: These data suggest that ACSS2 is an important factor for promoting RCC development and is essential for cell migration and invasion, which it promotes by increasing the expression of LAMP1. Taken together, these findings reveal a potential target for the diagnosis and treatment of RCC.

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Section: Cellular Physiology and Biochemistry Cellular Physiology Andsupporting

confidence: 74%

“…The expression of ACSS2 is emerging as one of the key factors that enable cells to maximally utilize acetate as a nutritional source [24].…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 99%

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Guo

Gui

2018

Cell Physiol Biochem

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“…Acetate metabolism provides a parallel pathway for acetylcoA production separate from conversion of citrate to acetyl-CoA by ATP citrate lyase (ACLY) and thus acetate allows for protein acetylation and lipogenesis independent of citrate conversation to acetyl-CoA. This pathway is essential in nutrient deprived tumor microenvironments and other diverse contexts but the origin of acetate has been unclear [8][9][10][11][12][13][14] . It has been postulated that acetate may be synthesized de novo in cells [15][16][17][18][19] but the pathways and quantitative reaction mechanisms through which this may occur are unknown.…”

Section: Introductionmentioning

confidence: 99%

De novo acetate production is coupled to central carbon metabolism in mammals

Liu

et al. 2018

Preprint

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In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology.peer-reviewed)

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“…In mammalian cells, acetyl coenzyme A is produced from pyruvate through the action of pyruvate dehydrogenase, from citrate through the action of adenosine triphosphate citrate lyase, or from acetate through the action of acetyl coenzyme A synthetase 1 or 2 (ACSS1 or ACSS2) (63). Acetate itself can be salvaged from extracellular space (62). ACSS2 is overexpressed in a variety of tumor types, including breast, ovary, lung, and metastatic prostate cancer, and ACSS2 expression is higher in high-grade than lowgrade gliomas (30,64,65).…”

Section: Acetate Metabolismmentioning

confidence: 99%

“…Acetyl coenzyme A is a key intermediate metabolite and can be used to produce energy, provide precursors for fatty acid synthesis (a process catalyzed by the enzyme fatty acid synthase [FASN]), and regulate gene expression through protein acetylation (62). In mammalian cells, acetyl coenzyme A is produced from pyruvate through the action of pyruvate dehydrogenase, from citrate through the action of adenosine triphosphate citrate lyase, or from acetate through the action of acetyl coenzyme A synthetase 1 or 2 (ACSS1 or ACSS2) (63).…”

Section: Acetate Metabolismmentioning

confidence: 99%

Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine

et al. 2017

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Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy.

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The metabolic fate of acetate in cancer

Cited by 254 publications

References 115 publications

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression

De novo acetate production is coupled to central carbon metabolism in mammals

Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine

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