Glutaminolysis and autophagy in cancer

Villar, Victor H.; Merhi, Faten; Djavaheri-Mergny, Mojgan; Durán, Raúl V.

doi:10.1080/15548627.2015.1053680

Cited by 104 publications

(119 citation statements)

References 144 publications

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“…Interestingly, autophagy, which may play positive or negative roles in anoikis and non-apoptotic cell death after detachment, is regulated by glutaminolysis as well, through mTORC complexes (25). Speculatively, GLUD1/α-ketoglutarate alterations due to EMT or GRHL2 may affect cell survival through these additional pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Glutaminolysis is a critical metabolic pathway on which tumors rely as a major alternate carbon source to glucose, with significant ramifications for cell proliferation, metabolic adaptability and cell survival (23–25). Following deamination of glutamine to produce glutamate, glutamate dehydrogenase-1 (GLUD1 or GDH1) generates the Krebs cycle intermediate α-ketoglutarate (α-KG), which is converted by the Krebs cycle to fumarate, an important cofactor for glutathione peroxidase enzymes.…”

Section: Introductionmentioning

confidence: 99%

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Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis

Farris

Pifer

Zheng

et al. 2016

Molecular Cancer Research

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Resistance to anoikis is a pre-requisite for tumor metastasis. The epithelial-to-mesenchymal transition (EMT) allows tumor cells to evade anoikis. The wound healing regulatory transcription factor Grainyhead-like 2 (GRHL2) suppresses/reverses EMT, accompanied by suppression of the cancer stem cell (CSC) phenotype and by re-sensitization to anoikis. Here, the effects of GRHL2 upon intracellular metabolism in the context of reversion of the EMT/CSC phenotype, with a view toward understanding how these effects promote anoikis sensitivity were investigated. EMT enhanced mitochondrial oxidative metabolism. While this was accompanied by higher accumulation of superoxide, the overall level of Reactive Oxygen Species (ROS) declined, due to decreased hydrogen peroxide. Glutamate Dehydrogenase 1 (GLUD1) expression increased in EMT, and this increase, via the product α-ketoglutarate (α-KG), was important for suppressing hydrogen peroxide and protecting against anoikis. GRHL2 suppressed GLUD1 gene expression, decreased α-KG, increased ROS and sensitized cells to anoikis. Implications These results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis

Farris

Pifer

Zheng

et al. 2016

Molecular Cancer Research

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“…Glutamine is the most abundant amino acid in the blood and a nitrogen source for cells78. This amino acid has been described as a crucial nutrient for tumour proliferation, and indeed a vast number of different types of tumour cells consume abnormally high quantities of glutamine and develop glutamine addiction9101112.…”

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confidence: 99%

mTORC1 inhibition in cancer cells protects from glutaminolysis-mediated apoptosis during nutrient limitation

et al. 2017

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A master coordinator of cell growth, mTORC1 is activated by different metabolic inputs, particularly the metabolism of glutamine (glutaminolysis), to control a vast range of cellular processes, including autophagy. As a well-recognized tumour promoter, inhibitors of mTORC1 such as rapamycin have been approved as anti-cancer agents, but their overall outcome in patients is rather poor. Here we show that mTORC1 also presents tumour suppressor features in conditions of nutrient restrictions. Thus, the activation of mTORC1 by glutaminolysis during nutritional imbalance inhibits autophagy and induces apoptosis in cancer cells. Importantly, rapamycin treatment reactivates autophagy and prevents the mTORC1-mediated apoptosis. We also observe that the ability of mTORC1 to activate apoptosis is mediated by the adaptor protein p62. Thus, the mTORC1-mediated upregulation of p62 during nutrient imbalance induces the binding of p62 to caspase 8 and the subsequent activation of the caspase pathway. Our data highlight the role of autophagy as a survival mechanism upon rapamycin treatment.

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“…In addition to the above, autophagy can solve therapy resistance and tumor relapse problems [24], take place in the heat shock response as well [25]. Autophagy is increased in many long lived model organisms and contributes significantly to their longevity [26].…”

Section: The Role Of Cell Autophagy In Nanomaterials Induced Toxicitymentioning

confidence: 99%

“…Autophagy has emerged as a mediator in the pathogenesis of RA [23]. The dual fuction of autophagy is also embodied in cancer sites it removes damaged organelles to avoid the accumulation of oxygen free radicals and mutation, but limit cell necrosis and the spread of inflammation, helping tumor cells survive in metabolic stress and immune suppression at the same time.In addition to the above, autophagy can solve therapy resistance and tumor relapse problems [24], take place in the heat shock response as well [25]. Autophagy is increased in many long lived model organisms and contributes significantly to their longevity [26].…”

mentioning

confidence: 99%

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

Wei¹

2017

NTMB

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NanomaterialsThe overview of nanomaterials Nanomaterials are defined as materials composed of unbound particles or particles in an aggregate or agglomerate state with one or more external dimensions with a size ranging from 1nm to 100nm [1]. Nanomaterials have a lot of free surfaces and interfaces and there is interaction between the various units. Based on the above characteristics, nanomaterials are featured by surface effect, small size effect, quantum size effect, macroscopic quantum tunneling effect and the dielectric confinement effect. Nanoparticles have lots of unpaired atoms, large specific surface area, less surface defects and can occur in conjunction with the polymer stronger physically or chemically. Added to the polymer material, they can improve the ductility, toughness, strength, barrier properties, heat resistance and dimensional stability of the material. They have been widely used in conventional materials, medical equipment, electronic equipment, paint and other industries. However, nanomaterials will affect the organism and produce a series of toxic effects by inducing oxidative stress and inflammatory response mechanisms in the cell, subcellular and protein levels. The nanomaterials commonly used in dentistryNanometer materials are widely applied in the field of dentistry, including dental restoration, antibacterial, caries treatment, orthodontic, root canal, bonding systems and so on.Adding nanoparticles to dental restoration materials to improve the performance has been widely used in the clinical field. In view of its unpaired atoms, large specific surface area, less surface defects and occurring in conjunction with the polymer either stronger physically or chemically, the novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano antibacterial inorganic fillers, there by leading to effective caries inhibition in dental application [2]. The mesoporous silica biomaterials have great potential for serving as both a catalyst and carrier in the repair or regeneration of dental hard tissue [3]. Diatomite-based nanocomposite ceramics are good potential candidates for ceramic-based dental materials [4]. Nano silicon dioxide can also give polymers the characteristics of better viscosity, thermal stability, high strength, less volume shrinkage and of course, durability [5].In clinical endodontics especially root canal and restorative treatments we can see the near future potential of nanoparticles from the application of nanoparticles in the form of solutions for irrigation, medication and as an additive within sealers/restorative materials [6]. GICs can be applied to base plates of Orthodontic and modified denture base well, as which contain chlorhexidine hexametaphosphate nanoparticles and characterize the nanoparticle size shows a stronger antimicrobial activity [7].As for caries treatment, Hannig M said that Analysis of in vitro data indicates that apatite nanoparticles might be effective in reversing lesion progression in the outer but not in the deepe...

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Glutaminolysis and autophagy in cancer

Cited by 104 publications

References 144 publications

Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis

Grainyhead-like 2 Reverses the Metabolic Changes Induced by the Oncogenic Epithelial–Mesenchymal Transition: Effects on Anoikis

mTORC1 inhibition in cancer cells protects from glutaminolysis-mediated apoptosis during nutrient limitation

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

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