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Glutamine cancer

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https://www.readbyqxmd.com/read/29221133/endogenous-glutamine-decrease-is-associated-with-pancreatic-cancer-progression
#1
Cecilia Roux, Chiara Riganti, Sammy Ferri Borgogno, Roberta Curto, Claudia Curcio, Valeria Catanzaro, Giuseppe Digilio, Sergio Padovan, Maria Paola Puccinelli, Monica Isabello, Silvio Aime, Paola Cappello, Francesco Novelli
Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217764/radiotherapy-activated-cancer-associated-fibroblasts-promote-tumor-progression-through-paracrine-igf-1r-activation
#2
Joke Tommelein, Elly De Vlieghere, Laurine Verset, Elodie Melsens, Justine Leenders, Benedicte Descamps, Annelies Debucquoy, Christian Vanhove, Patrick Pauwels, Christian P Gespach, Anne Vral, Astrid De Boeck, Karin Haustermans, Pascal de Tullio, Wim Ceelen, Pieter Demetter, Tom Boterberg, Marc Bracke, Olivier De Wever
Preoperative radiotherapy (RT) is a mainstay in the management of rectal cancer (RC), a tumor characterized by desmoplastic stroma containing cancer-associated fibroblasts (CAF). Although CAF are abundantly present, the effects of RT to CAF and its impact on cancer cells are unknown. We evaluated the damage responses of CAF to RT and investigated changes in colorectal cancer (CRC) cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from irradiated CAF. RT to CAF induced DNA damage, p53 activation, cell cycle arrest, and secretion of paracrine mediators including insulin-like growth factor-1 (IGF-1)...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212306/oncogene-driven-metabolic-alterations-in-cancer
#3
REVIEW
Hye-Young Min, Ho-Young Lee
Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212303/targeting-glutamine-metabolism-for-cancer-treatment
#4
REVIEW
Yeon-Kyung Choi, Keun-Gyu Park
Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212209/targeted-inhibition-of-glutaminase-as-a-potential-new-approach-for-the-treatment-of-nf1-associated-soft-tissue-malignancies
#5
Tahir N Sheikh, Parag P Patwardhan, Serge Cremers, Gary K Schwartz
Many cancer cells rely on glutamine as the source of carbon molecules to feed the biosynthetic pathways and are often addicted to glutaminolysis. Inhibitors of glutaminase activity have gained attention in the last few years due to their anti-proliferative effect and ability to induce apoptosis in some cancers. Although it is a promising therapeutic approach, its efficacy or the role played by glutamine in modulating cell proliferation in NF1 associated tumors has never been studied. We report for the first time, a strong correlation between the NF1 status of tumor cells and increased sensitivity to glutamine deprivation and glutaminase inhibition...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29208682/the-receptor-tyrosine-kinase-epha2-promotes-glutamine-metabolism-in-tumors-by-activating-the-transcriptional-coactivators-yap-and-taz
#6
Deanna N Edwards, Verra M Ngwa, Shan Wang, Eileen Shiuan, Dana M Brantley-Sieders, Laura C Kim, Albert B Reynolds, Jin Chen
Malignant tumors reprogram cellular metabolism to support cancer cell proliferation and survival. Although most cancers depend on a high rate of aerobic glycolysis, many cancer cells also display addiction to glutamine. Glutamine transporters and glutaminase activity are critical for glutamine metabolism in tumor cells. We found that the receptor tyrosine kinase EphA2 activated the TEAD family transcriptional coactivators YAP and TAZ (YAP/TAZ), likely in a ligand-independent manner, to promote glutamine metabolism in cells and mouse models of HER2-positive breast cancer...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29204729/-nutrient-sensing-and-self-renewal-o-glcnac-in-a-new-role
#7
REVIEW
Nikita S Sharma, Ashok K Saluja, Sulagna Banerjee
Whether embryonic, hematopoietic or cancer stem cells, this metabolic reprogramming is dependent on the nutrient-status and bioenergetic pathways that is influenced by the micro-environmental niches like hypoxia. Thus, the microenvironment plays a vital role in determining the stem cell fate by inducing metabolic reprogramming. Under the influence of the microenvironment, like hypoxia, the stem cells have increased glucose and glutamine uptake which result in activation of hexosamine biosynthesis pathway (HBP) and increased O-GlcNAc Transferase (OGT)...
December 5, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29202474/adhfe1-is-a-breast-cancer-oncogene-and-induces-metabolic-reprogramming
#8
Prachi Mishra, Wei Tang, Vasanta Putluri, Tiffany H Dorsey, Feng Jin, Fang Wang, Donewei Zhu, Lauren Amable, Tao Deng, Shaofei Zhang, J Keith Killian, Yonghong Wang, Tsion Z Minas, Harry G Yfantis, Dong H Lee, Arun Sreekumar, Michael Bustin, Wei Liu, Nagireddy Putluri, Stefan Ambs
Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival...
November 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29202102/combinatorial-treatment-with-natural-compounds-in-prostate-cancer-inhibits-prostate-tumor-growth-and-leads-to-key-modulations-of-cancer-cell-metabolism
#9
Alessia Lodi, Achinto Saha, Xiyuan Lu, Bo Wang, Enrique Sentandreu, Meghan Collins, Mikhail G Kolonin, John DiGiovanni, Stefano Tiziani
High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism...
2017: NPJ Precision Oncology
https://www.readbyqxmd.com/read/29180650/a-route-to-terahertz-metamaterial-biosensor-integrated-with-microfluidics-for-liver-cancer-biomarker-testing-in-early-stage
#10
Zhaoxin Geng, Xiong Zhang, Zhiyuan Fan, Xiaoqing Lv, Hongda Chen
Engineered Terahertz (THz) metamaterials presented an unique characteristics for biosensing application due to their accurately tunable resonance frequency, which is in accord with vibrational frequency of some important biomolecules such as cancer biomarker. However, water absorption in THz regime is an obstacle to extend application in trace biomolecules of cancer antibody or antigen. Here, to overcome water absorption and enhance the THz biosensing sensitivity, two kinds of THz metamaterials biosensor integrated with microfluidics were fabricated and used to detect the Alpha fetoprotein (AFP) and Glutamine transferase isozymes II (GGT-II) of liver cancer biomarker in early stage...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29172854/design-of-composite-microparticle-systems-based-on-pectin-and-waste-material-of-propolis-for-modified-l-alanyl-l-glutamine-release-and-with-immunostimulant-activity
#11
Mônica Villa Nova, Bianca A Ratti, Leandro S Herculano, Paulo R S Bittencourt, Cláudio R Novello, Roberto Barbosa Bazotte, Sueli de Oliveira Silva Lautenschlager, Marcos Luciano Bruschi
Catabolic conditions like acquired immunodeficiency syndrome, cancer and burn can cause immunosuppression. Amino acids such as alanine and glutamine are essential for the activity of the immune system. Propolis is immunostimulant and the waste of propolis extraction has been reused with technological and therapeutic purposes. Therefore, this study describes the association of propolis byproduct extract with pectin to prepare spray-dried microparticles containing the dipeptide L-alanyl-L-glutamine as stimulant systems of neutrophils...
November 27, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29170516/metabolic-differences-in-glutamine-utilization-lead-to-metabolic-vulnerabilities-in-prostate-cancer
#12
Niki Marie Zacharias, Christopher McCullough, Sriram Shanmugavelandy, Jaehyuk Lee, Youngbok Lee, Prasanta Dutta, James McHenry, Linda Nguyen, William Norton, Lawrence W Jones, Pratip K Bhattacharya
The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29169183/myc-regulation-of-glutamine-proline-regulatory-axis-is-key-in-luminal-b-breast-cancer
#13
Madeleine L Craze, Hayley Cheung, Natasha Jewa, Nuno D M Coimbra, Daniele Soria, Rokaya El-Ansari, Mohammed A Aleskandarany, Kiu Wai Cheng, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Emad A Rakha, Andrew R Green
BACKGROUND: Altered cellular metabolism is a hallmark of cancer and some are reliant on glutamine for sustained proliferation and survival. We hypothesise that the glutamine-proline regulatory axis has a key role in breast cancer (BC) in the highly proliferative classes. METHODS: Glutaminase (GLS), pyrroline-5-carboxylate synthetase (ALDH18A1), and pyrroline-5-carboxylate reductase 1 (PYCR1) were assessed at DNA/mRNA/protein levels in large, well-characterised cohorts...
November 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29163707/n-myc-downstream-regulated-gene-2-restrains-glycolysis-and-glutaminolysis-in-clear-cell-renal-cell-carcinoma
#14
Wei Shi, Xinyuan Xu, Fei Yan, Bao Wang, Hang Zhao, Aaron Chan, Zhen Ren, Yongzheng Ma, Fuli Wang, Jianlin Yuan
Glycolysis and glutaminolysis are heavily involved in the metabolic reprogramming of cancer cells. The activation of oncogenes and inactivation of tumor suppressor genes has a marked effect on the cellular metabolic processes glycolysis and glutaminolysis. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene that previous studies have demonstrated can inhibit the growth, proliferation and metastasis of clear cell renal cell carcinoma (ccRCC) cells. However, the function of NDRG2 in ccRCC metabolism remains unknown...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163679/identification-of-molecular-mechanisms-of-glutamine-in-pancreatic-cancer
#15
Zhen-Yi Jia, Tong-Yi Shen, Wei Jiang, Huan-Long Qin
The aim of the present study was to explore the critical genes and molecular mechanisms in pancreatic cancer (PC) cells with glutamine. By analyzing microarray data GSE17632 from the Gene Expression Omnibus database, the DEGs between PC cells treated with glutamine and without glutamine were evaluated. Additionally, function enrichment analyses and protein-protein interaction (PPI) network construction of DEGs were performed. Network module and literature mining analyses were performed to analyze the critical DEGs in PC cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29159872/the-dark-side-of-glucose-transporters-in-prostate-cancer-are-they-a-new-feature-to-characterize-carcinomas
#16
REVIEW
Pedro Gonzalez-Menendez, David Hevia, Juan C Mayo, Rosa M Sainz
One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29158891/overexpression-of-hypoxia-inducible-factor-and-metabolic-pathways-possible-targets-of-cancer
#17
REVIEW
Davinder Singh, Rohit Arora, Pardeep Kaur, Balbir Singh, Rahul Mannan, Saroj Arora
Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29153487/endothelial-cell-metabolism-in-health-and-disease
#18
REVIEW
Katerina Rohlenova, Koen Veys, Ines Miranda-Santos, Katrien De Bock, Peter Carmeliet
The metabolism of endothelial cells (ECs) has only recently been recognized as a driving force of angiogenesis. Metabolic pathways, such as glycolysis, fatty acid oxidation, and glutamine metabolism, have distinct, essential roles during vessel formation. Moreover, EC metabolism is markedly perturbed in pathologies such as cancer and diabetes. For instance, because tumor ECs increase glycolysis, lowering hyperglycolysis in tumor ECs induces therapeutic benefits in preclinical tumor models. Expanding our knowledge of how ECs alter their metabolism in disease could pave the way for novel therapeutic opportunities...
November 16, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/29151270/asct2-defined-by-enzyme-mediated-activation-of-radical-sources-enhances-malignancy-of-gd2-plus-small-cell-lung-cancer
#19
Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa
Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Consequently, we identified ASC amino-acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2...
November 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/29146184/glutamate-production-from-ammonia-via-glutamate-dehydrogenase-2-activity-supports-cancer-cell-proliferation-under-glutamine-depletion
#20
Yukiko Takeuchi, Yasumune Nakayama, Eiichiro Fukusaki, Yasuhiro Irino
Cancer cells rapidly consume glutamine as a carbon and nitrogen source to support proliferation, but the cell number continues to increase exponentially after glutamine is nearly depleted from the medium. In contrast, cell proliferation rates are strongly depressed when cells are cultured in glutamine-free medium. How cancer cells survive in response to nutrient limitation and cellular stress remains poorly understood. In addition, rapid glutamine catabolism yields ammonia, which is a potentially toxic metabolite that is secreted into the extracellular space...
November 13, 2017: Biochemical and Biophysical Research Communications
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