CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer

Han, Susan S.; Wei, Ryan; Zhang, Xiaodi; Jiang, Nian; Fan, Ming; Huang, Jie; Xie, Bowen; Zhang, Lu; Miao, Weili; Butler, Ashley Chen Ping; Coleman, Matthew A.; Vaughan, Andrew T M; Wang, Yinsheng; Chen, Hong Wu; Liu, Jiankang; Li, Jian Jian

doi:10.3389/fonc.2019.01201

Cited by 104 publications

(72 citation statements)

References 54 publications

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“…Lee et al have demonstrated that c-myc and mitochondrial protein Mcl1 cooperate to activate OXPHOS in breast cancer CSCs, thereby promoting drug resistance and tumor formation [ 62 ]. FAO has also been shown to activate OXPHOS in CSCs by supplying acetyl-CoA in the TCA cycle [ 89 , 130 , 138 ]. Han et al demonstrated that carnitine palmitoyltransferase 1A and 2, which are FAO rate-limiting enzymes, enhance the tolerance to radiation of breast cancer cells by enhancing ATP production by FAO [ 138 ].…”

Section: Metabolism Of Cscsmentioning

confidence: 99%

“…FAO has also been shown to activate OXPHOS in CSCs by supplying acetyl-CoA in the TCA cycle [ 89 , 130 , 138 ]. Han et al demonstrated that carnitine palmitoyltransferase 1A and 2, which are FAO rate-limiting enzymes, enhance the tolerance to radiation of breast cancer cells by enhancing ATP production by FAO [ 138 ]. Furthermore, Citrate, which is generated from FAO-derived acetyl-CoA, is oxidized to α-ketoglutarate or pyruvate in cytoplasm and produces cytosolic NADPH [ 83 ].…”

Section: Metabolism Of Cscsmentioning

confidence: 99%

“…The glutaminase inhibitors BPTES and CB839 strongly inhibit the growth of glutamine-addicted tumors even when used alone, but they have been shown to be more potent when combined with other metabolic inhibitors or conventional chemotherapy [ 68 , 69 , 70 , 171 , 178 , 179 ]. The FAO inhibitor etomoxir also enhanced the therapeutic effect of conventional chemotherapy in several types of cancers in vivo [ 138 , 180 , 181 ]. The selective Nrf2 inhibitor trigonelline, the xCT inhibitor sulfasalazine, the GSH inhibitor buthionine sulfoximine, and the Trx inhibitor auranofin induce cell death by accumulating ROS in CSCs.…”

Section: Therapeutic Strategies For Targeting Csc Metabolismmentioning

confidence: 99%

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The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Tanabe

Sahara

2020

Cancers

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Numerous findings have indicated that CSCs, which are present at a low frequency inside primary tumors, are the main cause of therapy resistance and cancer recurrence. Although various therapeutic methods targeting CSCs have been attempted for eliminating cancer cells completely, the complicated characteristics of CSCs have hampered such attempts. In analyzing the biological properties of CSCs, it was revealed that CSCs have a peculiar metabolism that is distinct from non-CSCs to maintain their stemness properties. The CSC metabolism involves not only the catabolic and anabolic pathways, but also intracellular signaling, gene expression, and redox balance. In addition, CSCs can reprogram their metabolism to flexibly respond to environmental changes. In this review, we focus on the flexible metabolic mechanisms of CSCs, and highlight the new therapeutics that target CSC metabolism.

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Section: Metabolism Of Cscsmentioning

confidence: 99%

Section: Metabolism Of Cscsmentioning

confidence: 99%

Section: Therapeutic Strategies For Targeting Csc Metabolismmentioning

confidence: 99%

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The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Tanabe

Sahara

2020

Cancers

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“…Previous studies demonstrated that mitochondrial activity, which is critical for T-cell function, can be augmented by blocking PD1 or CTLA4 signaling, which consequently overcomes T-cell exhaustion ( 44 ). PD1 has been shown to affect T cells by prompting metabolic reprogramming toward depressed glycolysis and increased FAO, as well as increasing the expression of carnitine palmitoyl transferase 1A (CPT1A), which promotes the FAO of endogenous lipids ( 48 ). On the other hand, CTLA4 acts on T cells by inhibiting glycolysis with no augmentation of FAO ( 49 ).…”

Section: Immune Checkpoint Inhibitors and Mitochondrial Metabolismmentioning

confidence: 99%

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches

Klein

Younes

et al. 2020

Front. Immunol.

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The role of mitochondria in cancer formation and progression has been studied extensively, but much remains to be understood about this complex relationship. Mitochondria regulate many processes that are known to be altered in cancer cells, from metabolism to oxidative stress to apoptosis. Here, we review the evolving understanding of the role of mitochondria in cancer cells, and highlight key evidence supporting the role of mitochondria in cancer immune evasion and the effects of mitochondria-targeted antitumor therapy. Also considered is how knowledge of the role of mitochondria in cancer can be used to design and improve cancer therapies, particularly immunotherapy and radiation therapy. We further offer critical insights into the mechanisms by which mitochondria influence tumor immune responses, not only in cancer cells but also in immune cells. Given the central role of mitochondria in the complex interactions between cancer and the immune system, high priority should be placed on developing rational strategies to address mitochondria as potential targets in future preclinical and clinical studies. We believe that targeting mitochondria may provide additional opportunities in the development of novel antitumor therapeutics.

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“…Increased expression or abnormal activity of key lipogenic enzymes such as fatty acid synthase (FASN) and acetyl coenzyme A (acetyl-CoA) carboxylase is often attributed to the high growth rate and lipogenic phenotype of tumor cells ( 76 – 80 ). Moreover, carnitine palmitoyl transferase (CPT) 1 and 2, which are rate-limiting enzymes involved in mitochondrial fatty acid transportation, play crucial roles in increasing fatty acid oxidation required for the cellular fuel demands of breast cancer cells ( 81 ). CPT1A/CPT2 were highly expressed in recurrent human breast cancers and are associated with poor prognosis.…”

Section: Lipid Metabolism With Lncrnamentioning

confidence: 99%

Long Non-coding RNAs Involved in Metabolic Alterations in Breast and Prostate Cancers

et al. 2020

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Breast and prostate cancers are the most prevalent cancers in females and males, respectively. These cancers exhibit sex hormone dependence and thus, hormonal therapies are used to treat these cancers. However, acquired resistance to hormone therapies is a major clinical problem. In addition, certain portions of these cancers initially exhibit hormone-independence due to the absence of sex hormone receptors. Therefore, precise and profound understanding of the cancer pathophysiology is required to develop novel clinical strategies against breast and prostate cancers. Metabolic reprogramming is currently recognized as one of the hallmarks of cancer, as exemplified by the alteration of glucose metabolism, oxidative phosphorylation, and lipid metabolism. Dysregulation of metabolic enzymes and their regulators such as kinases, transcription factors, and other signaling molecules contributes to metabolic alteration in cancer. Moreover, accumulating lines of evidence reveal that long non-coding RNAs (lncRNAs) regulate cancer development and progression by modulating metabolism. Understanding the mechanism and function of lncRNAs associated with cancer-specific metabolic alteration will therefore provide new knowledge for cancer diagnosis and treatment. This review provides an overview of recent studies regarding the role of lncRNAs in metabolism in breast and prostate cancers, with a focus on both sex hormone-dependent and -independent pathways.

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CPT1A/2-Mediated FAO Enhancement—A Metabolic Target in Radioresistant Breast Cancer

Cited by 104 publications

References 54 publications

The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells

Role of Mitochondria in Cancer Immune Evasion and Potential Therapeutic Approaches

Long Non-coding RNAs Involved in Metabolic Alterations in Breast and Prostate Cancers

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