Erratum: From Krebs to clinic: glutamine metabolism to cancer therapy

Altman, Brian J.; Stine, Zachary E.; Dang, Chi V.

doi:10.1038/nrc.2016.131

Cited by 64 publications

(29 citation statements)

References 1 publication

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“…Thus, the xCT system is key regulator of cancer cells redox balance, while its inactivation might sensitize malignant cells to OS inducers. Of note, xCT overexpression is expected to promote glutamine catabolism to support TCA cycle anaplerosis or GSH synthesis [254]. In this respect, a recent study from Sayin et al, reported that LOF mutations of the KEAP1 gene can mediate glutamine addiction in both mouse (KPK) and human KRAS-driven LUAD cell lines.…”

Section: Nrf2 Regulates Metabolic Processes Leading To Gsh Synthesis mentioning

confidence: 99%

“…Thus, oncogenic alterations in the NRF2-KEAP1 axis can induce defects in central carbon metabolism of cancer cells and reveal metabolic vulnerabilities that can be targeted. Notably, glutamine is the most abundant aminoacid in human serum and is essential for many cancer cells to generate TCA cycle intermediates and support the biosynthesis of nucelotides, N-acetyl glucosamines, fatty acids, GSH and other aminoacids [254]. Intriguingly, NRF2 can control different steps of glutamine fate, from its uptake to its metabolism.…”

Section: Nrf2 Regulates Metabolic Processes Leading To Gsh Synthesis mentioning

confidence: 99%

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Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.

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Section: Nrf2 Regulates Metabolic Processes Leading To Gsh Synthesis mentioning

confidence: 99%

Section: Nrf2 Regulates Metabolic Processes Leading To Gsh Synthesis mentioning

confidence: 99%

Potential Applications of NRF2 Modulators in Cancer Therapy

et al. 2020

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“…Rather than utilizing the normal process of oxidative phosphorylation, even with the presence of oxygen and fully functioning mitochondria, these proliferating cancer cells favor aerobic glycolysis, which dramatically increases the uptake of glucose and production of lactate; a process known as the Warburg Effect . Glutamine metabolism also plays a vital role in cancer cell energy metabolism by providing Krebs cycle intermediates, which further corroborates the idea of altered cancer cell metabolism . Most cancers depend on increased glutaminolysis to compensate for increased energy needs and fill their carbon and nitrogen pools for the biosynthesis of macromolecules .…”

Section: Introductionmentioning

confidence: 74%

Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism

et al. 2019

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Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the CENPF network, additional associations with lipid regulation are found. Further untargeted metabolomics analysis using gas chromatography-time-of-flight-mass spectrometry reveals that silencing of CENPF alters the global metabolic profiles of PC cells and inhibits cell proliferation, which suggests that CENPF may be a critical regulator of PC metabolism. These findings provide useful scientific insights that can be applied in future studies investigating potential targets for PC treatment.

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“…Glucose metabolism rewiring is more likely to be driven by an elevated demand of reducing equivalents and molecular precursors of proteins, nucleotides and lipids, which are the building blocks required to maintain cancer cell growth and proliferation [11]. Besides glucose, glutamine also contributes to core metabolic functions of cancer cells since it fuels the tricarboxylic acid (TCA) cycle, nucleotide and fatty acid biosynthesis and redox balance [10,12], replacing completely glucose as a core organic compound.…”

Section: Cancer Metabolismmentioning

confidence: 99%

Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

Mendes

Serpa

2019

Antioxidants

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Metabolic remodelling is a hallmark of cancer, however little has been unravelled in its role in chemoresistance, which is a major hurdle to cancer control. Lung cancer is a leading cause of death by cancer, mainly due to the diagnosis at an advanced stage and to the development of resistance to therapy. Targeted therapeutic agents combined with comprehensive drugs are commonly used to treat lung cancer. However, resistance mechanisms are difficult to avoid. In this review, we will address some of those therapeutic regimens, resistance mechanisms that are eventually developed by lung cancer cells, metabolic alterations that have already been described in lung cancer and putative new therapeutic strategies, and the integration of conventional drugs and genetic and metabolic-targeted therapies. The oxidative stress is pivotal in this whole network. A better understanding of cancer cell metabolism and molecular adaptations underlying resistance mechanisms will provide clues to design new therapeutic strategies, including the combination of chemotherapeutic and targeted agents, considering metabolic intervenients. As cancer cells undergo a constant metabolic adaptive drift, therapeutic regimens must constantly adapt.

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Erratum: From Krebs to clinic: glutamine metabolism to cancer therapy

Cited by 64 publications

References 1 publication

Potential Applications of NRF2 Modulators in Cancer Therapy

Potential Applications of NRF2 Modulators in Cancer Therapy

Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism

Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer

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