Acetyl-CoA Synthetase 2 as a Therapeutic Target in Tumor Metabolism

Liu, Mengfang; Liu, Na; Wang, Jinlei; Fu, Shengqiao; Wang, Xu; Chen, Deyu

doi:10.3390/cancers14122896

Cited by 22 publications

(13 citation statements)

References 112 publications

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“…19 Enzymes involved in Leu metabolism pathways, such as Leu transaminase branched-chain amino acid transaminase 1 (BCAT1) and acetyl-CoA synthetase (ACSS2), are also associated with breast cancer development and metastasis. [20][21][22]…”

Section: Leucinementioning

confidence: 99%

“…Silencing LLGL2 can diminish the activation of the mTOR pathway triggered by amino acid stimulation, and it is also implicated in breast cancer cells’ resistance to tamoxifen 19 . Enzymes involved in Leu metabolism pathways, such as Leu transaminase branched‐chain amino acid transaminase 1 (BCAT1) and acetyl‐CoA synthetase (ACSS2), are also associated with breast cancer development and metastasis 20–22 …”

Section: Eaas In Breast Cancermentioning

confidence: 99%

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Amino acids and their roles in tumor immunotherapy of breast cancer

Xia,

Zhu,

Zheng

et al. 2023

The Journal of Gene Medicine

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Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple‐negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune‐suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor‐specific or oncogene‐dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

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Section: Leucinementioning

confidence: 99%

Section: Eaas In Breast Cancermentioning

confidence: 99%

Amino acids and their roles in tumor immunotherapy of breast cancer

Xia,

Zhu,

Zheng

et al. 2023

The Journal of Gene Medicine

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“…In addition, acetyl-CoA synthetase 2 (ACSS2) can convert cytosolic acetate to acetyl-CoA for de novo fatty acid and cholesterol synthesis ( Figure 1 ) to promote tumor growth [ 1 ]. ACSS2 is upregulated in GBM [ 41 ] and in hepatocellular carcinoma (HCC), myeloma, prostate, and bladder cancers [ 42 ]. Furthermore, acetyl-CoA is also involved in epigenetic regulation as it enters into the nucleus to modify histone proteins by direct acetylation [ 43 ].…”

Section: Lipid Metabolism Regulation In Gbmmentioning

confidence: 99%

Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

2022

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Glioblastoma (GBM) is the most lethal primary brain tumor. With limited therapeutic options, novel therapies are desperately needed. Recent studies have shown that GBM acquires large amounts of lipids for rapid growth through activation of sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that regulates fatty acid and cholesterol synthesis, and cholesterol uptake. Interestingly, GBM cells divert substantial quantities of lipids into lipid droplets (LDs), a specific storage organelle for neutral lipids, to prevent lipotoxicity by increasing the expression of diacylglycerol acyltransferase 1 (DGAT1) and sterol-O-acyltransferase 1 (SOAT1), which convert excess fatty acids and cholesterol to triacylglycerol and cholesteryl esters, respectively. In this review, we will summarize recent progress on our understanding of lipid metabolism regulation in GBM to promote tumor growth and discuss novel strategies to specifically induce lipotoxicity to tumor cells through disrupting lipid storage, a promising new avenue for treating GBM.

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“…Specifically, mitochondria-localized acetyl-CoA synthetases (ACSS 1/2) convert acetate into acetyl-CoA for use in the TCA cycle or fatty acid synthesis [70]. The abnormal expression of ACSS2 has also been observed in several cancers, making it a potential target for cancer therapy [71][72][73]. Acetate, in addition to serving as a buffer for metabolic intermediates, can also play the function of compensating for acidic PH environments through its role in histone acetylation [70].…”

Section: Acetatementioning

confidence: 99%

Application of Metabolic Reprogramming to Cancer Imaging and Diagnosis

Yang

Cai

et al. 2022

IJMS

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Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate.

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Acetyl-CoA Synthetase 2 as a Therapeutic Target in Tumor Metabolism

Cited by 22 publications

References 112 publications

Amino acids and their roles in tumor immunotherapy of breast cancer

Amino acids and their roles in tumor immunotherapy of breast cancer

Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

Application of Metabolic Reprogramming to Cancer Imaging and Diagnosis

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