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https://www.readbyqxmd.com/read/30334010/translating-metabolic-reprogramming-into-new-targets-for-kidney-cancer
#1
Omran Abu Aboud, Robert H Weiss
In the age of bioinformatics and with the advent of high-powered computation over the past decade or so the landscape of biomedical research has become radically altered. Whereas a generation ago, investigators would study their "favorite" protein or gene and exhaustively catalog the role of this compound in their disease of interest, the appearance of omics has changed the face of medicine such that much of the cutting edge (and fundable!) medical research now evaluates the biology of the disease nearly in its entirety...
November 27, 2017: Kidney cancer
https://www.readbyqxmd.com/read/30333826/enzymatic-inactivation-of-oxysterols-in-breast-tumor-cells-constraints-metastasis-formation-by-reprogramming-the-metastatic-lung-microenvironment
#2
Marta A Moresco, Laura Raccosta, Gianfranca Corna, Daniela Maggioni, Matias Soncini, Silvio Bicciato, Claudio Doglioni, Vincenzo Russo
Recent evidence indicates that immune cells contribute to the formation of tumor metastases by regulating the pre-metastatic niche. Whether tumor-derived factors involved in primary tumor formation play a role in metastasis formation is poorly characterized. Oxysterols act as endogenous regulators of lipid metabolism through the interaction with the nuclear Liver X Receptors-(LXR)α and LXRβ. In the context of tumor development, they establish a pro-tumor environment by dampening antitumor immune responses, and by recruiting pro-angiogenic and immunosuppressive neutrophils...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30327492/publisher-correction-mycobacterium-tuberculosis-carrying-a-rifampicin-drug-resistance-mutation-reprograms-macrophage-metabolism-through-cell-wall-lipid-changes
#3
Nicole C Howard, Nancy D Marin, Mushtaq Ahmed, Bruce A Rosa, John Martin, Monika Bambouskova, Alexey Sergushichev, Ekaterina Loginicheva, Natalia Kurepina, Javier Rangel-Moreno, Liang Chen, Barry N Kreiswirth, Robyn S Klein, Joan-Miquel Balada-Llasat, Jordi B Torrelles, Gaya K Amarasinghe, Makedonka Mitreva, Maxim N Artyomov, Fong-Fu Hsu, Barun Mathema, Shabaana A Khader
In the version of this Letter originally published, in Fig. 2d, in the third graph, the label for the y axis was incorrect as 'TNF-α (pg ml-1 )'; it should have read 'IL-1β (pg ml-1 )'. This has now been corrected.
October 16, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/30327195/rbm4a-modulates-the-impact-of-prdm16-on-development-of-brown-adipocytes-through-an-alternative-splicing-mechanism
#4
Yi-Lin Chi, Jung-Chun Lin
Brown adipocytes (BAs) exhibit an energy-expending signature that is important in balancing metabolic homeostasis. In this study, results of transcriptome analyses revealed the reprogrammed splicing profile of the PR domain containing 16 (PRDM16) gene, a key transcription factor involved in brown adipogenesis, throughout development of wild-type brown adipose tissues (BATs). Moreover, discriminative splicing patterns of PRDM16 transcripts were noted in embryonic and postnatal RBM4a-/- BATs. Overexpression of RBM4a enhanced the relative levels of PRDM16-ex 16 transcripts by simultaneously interacting with exonic and intronic CU elements, which encoded the PRDM16S isoform containing a distinct C-terminus...
November 2018: Biochimica et biophysica acta. Molecular cell research
https://www.readbyqxmd.com/read/30322894/infiltrative-and-drug-resistant-slow-cycling-cells-support-metabolic-heterogeneity-in-glioblastoma
#5
Lan B Hoang-Minh, Florian A Siebzehnrubl, Changlin Yang, Silveli Suzuki-Hatano, Kyle Dajac, Tyler Loche, Nicholas Andrews, Michael Schmoll Massari, Jaimin Patel, Krisha Amin, Alvin Vuong, Ana Jimenez-Pascual, Paul Kubilis, Timothy J Garrett, Craig Moneypenny, Christina A Pacak, Jianping Huang, Elias J Sayour, Duane A Mitchell, Matthew R Sarkisian, Brent A Reynolds, Loic P Deleyrolle
Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions...
October 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/30321589/epigenetic-upregulation-and-functional-role-of-the-mitochondrial-aspartate-glutamate-carrier-isoform-1-in-hepatocellular-carcinoma
#6
Vittoria Infantino, Francesco Dituri, Paolo Convertini, Anna Santarsiero, Ferdinando Palmieri, Simona Todisco, Serena Mancarella, Gianluigi Giannelli, Vito Iacobazzi
Metabolic reprogramming is a common hallmark of cancer cells. Although some biochemical features have been clarified, there is still much to learn about cancer cell metabolism and its regulation. Aspartate-glutamate carrier isoform 1 (AGC1), encoded by SLC25A12 gene, catalyzes an exchange between intramitochondrial aspartate and cytosolic glutamate plus a proton across the mitochondrial membrane, so supplying aspartate to the cytosol. SLC25A12, expressed in brain, heart, and skeletal muscle, is silenced in normal liver...
October 12, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30320908/-1-h-nmr-metabolomics-reveals-increased-glutaminolysis-upon-overexpression-of-nsd3s-or-pdp3-in-saccharomyces-cerevisiae
#7
Germana B Rona, Natalia P Almeida, Gilson C Santos, Tatiana Ks Fidalgo, Fabio Cl Almeida, Elis Ca Eleutherio, Anderson S Pinheiro
NSD3s, the proline-tryptophan-tryptophan-proline (PWWP) domain-containing, short isoform of the human oncoprotein NSD3, displays high transforming properties. Overexpression of human NSD3s or the yeast protein Pdp3 in Saccharomyces cerevisiae induces similar metabolic changes, including increased growth rate and sensitivity to oxidative stress, accompanied by decreased oxygen consumption. Here, we set out to elucidate the biochemical pathways leading to the observed metabolic phenotype by analyzing the alterations in yeast metabolome in response to NSD3s or Pdp3 overexpression using 1 H nuclear magnetic resonance (NMR) metabolomics...
October 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30320488/cd147-mediated-glucose-metabolic-regulation-contributes-to-the-predictive-role-of-18-f-fdg-pet-ct-imaging-for-egfr-tki-treatment-sensitivity-in-nsclc
#8
Xiaofeng Li, Qiang Fu, Yanjia Zhu, Jian Wang, Jianjing Liu, Xiaozhou Yu, Wengui Xu
The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via western blotting and flow cytometric analyses. Radioactive uptake of 18 F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming...
October 15, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/30320378/mst1-regulates-non-small-cell-lung-cancer-a549-cell-apoptosis-by-inducing-mitochondrial-damage-via-rock1-f%C3%A2-actin-pathways
#9
Weiqiang Zhang, Keiqiang Liu, Yingxin Pei, Jingbo Ma, Jiang Tan, Jing Zhao
Mammalian STE20-like kinase 1 (Mst1) is well recognized as a major tumor suppressor in cancer development, growth, metabolic reprogramming, metastasis, cell death and recurrence. However, the roles of Mst1 in non-small cell lung cancer (NSCLC) A549 cell phenotypic alterations remain to be elucidated. The present study aimed to explore the functional role and underlying mechanisms of Mst1 with regards to A549 cell proliferation, migration and apoptosis; this study focused on mitochondrial homeostasis and Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/F‑actin pathways...
October 8, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/30315468/determining-macrophage-polarization-upon-metabolic-perturbation
#10
Pu-Ste Liu, Ping-Chih Ho
Metabolic reprograming controlling macrophage activation and function is emerging as new regulatory circuit on shaping immune responses. Generally, lipopolysaccharides (LPS)-induced pro-inflammatory activated macrophages, known as M1 macrophages, display higher glycolysis. In contrast, interleukin-4 (IL-4)-skewed anti-inflammatory activated macrophages, known as M2 macrophages, mainly rely on oxidative phosphorylation for their bioenergetic demands. Emerging evidence reveals that these metabolic preferences further fine-tune macrophage polarization process, including signaling cascades and epigenetic reprogramming...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30315466/determining-the-impact-of-metabolic-nutrients-on-autophagy
#11
Jessica D Guillaume, Stephanie L Celano, Katie R Martin, Jeffrey P MacKeigan
Tumorigenesis relies on the ability of cancer cells to obtain necessary nutrients and fulfill increased energy demands associated with rapid proliferation. However, as a result of increased metabolite consumption and poor vascularization, most cancer cells must survive in a nutrient poor and high cellular stress microenvironment. Cancer cells undergo metabolic reprogramming to evade cell death and ensure proliferation; in particular, cancer cells utilize the catabolic process of autophagy. Autophagy creates an intracellular pool of metabolites by sequestering cytosolic macromolecules in double-membrane vesicles targeted for lysosomal degradation...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30312463/impairment-of-peroxisomal-apx-and-cat-activities-increases-protection-of-photosynthesis
#12
Rachel H V Sousa, Fabricio E L Carvalho, Yugo Lima-Melo, Vicente T C B Alencar, Danilo M Daloso, Marcia Margis-Pinheiro, Setsuko Komatsu, Joaquim A G Silveira
Retrograde signalling pathways, triggered by changes in cellular redox homeostasis, remain poorly understood. Transformed rice plants that are deficient in peroxisomal APX4 (RNAiOsAPX4) exhibit more effective protection of photosynthesis than controls when catalase (CAT) is inhibited, but the mechanisms involved have not been characterised. An in-depth physiological and proteomics analysis was therefore performed on the RNAiOsAPX4-CAT-inhibited rice plants. Loss of APX4 function led to an increased abundance of several proteins that are involved in essential metabolic pathways, possibly as a result of increased tissue H2O2 levels...
October 12, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/30312004/therapeutic-targeting-of-cellular-stress-responses-in-cancer
#13
REVIEW
Miao Chen, Songbo Xie
Similar to bacteria, yeast, and other organisms that have evolved pathways to respond to environmental stresses, cancer cells develop mechanisms that increase genetic diversity to facilitate adaptation to a variety of stressful conditions, including hypoxia, nutrient deprivation, exposure to DNA-damaging agents, and immune responses. To survive, cancer cells trigger mechanisms that drive genomic instability and mutation, alter gene expression programs, and reprogram the metabolic pathways to evade growth inhibition signaling and immune surveillance...
October 12, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/30311994/chlamydia-trachomatis-targets-mitochondrial-dynamics-to-promote-intracellular-survival-and-proliferation
#14
Yusuke Kurihara, Ryota Itoh, Akinori Shimizu, Nirwana Fitriani Walenna, Bin Chou, Kazunari Ishii, Toshinori Soejima, Aya Fujikane, Kenji Hiromatsu
Chlamydia trachomatis is an obligate intracellular bacterium that scavenges host metabolic products for its replication. Mitochondria are the power plants of eukaryotic cells and provide most of the cellular ATP via oxidative phosphorylation. Several intracellular pathogens target mitochondria as part of their obligatory cellular reprogramming. This study was designed to analyze the mitochondrial morphological changes in response to C. trachomatis infection in HeLa cells. Mitochondrial elongation and fragmentation were found at the early stages and late stages of C...
October 12, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/30311911/chromatin-mapping-identifies-basr-a-key-regulator-of-bacteria-triggered-production-of-fungal-secondary-metabolites
#15
Juliane Fischer, Sebastian Y Müller, Tina Netzker, Nils Jäger, Agnieszka Gacek-Matthews, Kirstin Scherlach, Maria C Stroe, María García-Altares, Francesco Pezzini, Hanno Schoeler, Michael Reichelt, Jonathan Gershenzon, Mario Kc Krespach, Ekaterina Shelest, Volker Schroeckh, Vito Valiante, Thorsten Heinzel, Christian Hertweck, Joseph Strauss, Axel A Brakhage
The eukaryotic epigenetic machinery can be modified by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. We discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster in the fungus Aspergillus nidulans . Using this model we aim at understanding mechanisms of microbial communication based on bacteria-triggered chromatin modification. By genome-wide ChIP-seq analysis of acetylated histone H3 we uncovered the unique chromatin landscape in A...
October 12, 2018: ELife
https://www.readbyqxmd.com/read/30306093/viral-and-nonviral-engineering-of-natural-killer-cells-as-emerging-adoptive-cancer-immunotherapies
#16
REVIEW
Sandro Matosevic
Natural killer (NK) cells are powerful immune effectors whose antitumor activity is regulated through a sophisticated network of activating and inhibitory receptors. As effectors of cancer immunotherapy, NK cells are attractive as they do not attack healthy self-tissues nor do they induce T cell-driven inflammatory cytokine storm, enabling their use as allogeneic adoptive cellular therapies. Clinical responses to adoptive NK-based immunotherapy have been thwarted, however, by the profound immunosuppression induced by the tumor microenvironment, particularly severe in the context of solid tumors...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/30305738/ire1%C3%AE-xbp1-controls-t-cell-function-in-ovarian-cancer-by-regulating-mitochondrial-activity
#17
Minkyung Song, Tito A Sandoval, Chang-Suk Chae, Sahil Chopra, Chen Tan, Melanie R Rutkowski, Mahesh Raundhal, Ricardo A Chaurio, Kyle K Payne, Csaba Konrad, Sarah E Bettigole, Hee Rae Shin, Michael J P Crowley, Juan P Cerliani, Andrew V Kossenkov, Ievgen Motorykin, Sheng Zhang, Giovanni Manfredi, Dmitriy Zamarin, Kevin Holcomb, Paulo C Rodriguez, Gabriel A Rabinovich, Jose R Conejo-Garcia, Laurie H Glimcher, Juan R Cubillos-Ruiz
Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4 . However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8 -induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function...
October 2018: Nature
https://www.readbyqxmd.com/read/30304688/real-time-imaging-of-mitochondrial-atp-dynamics-reveals-the-metabolic-setting-of-single-cells
#18
Maria R Depaoli, Felix Karsten, Corina T Madreiter-Sokolowski, Christiane Klec, Benjamin Gottschalk, Helmut Bischof, Emrah Eroglu, Markus Waldeck-Weiermair, Thomas Simmen, Wolfgang F Graier, Roland Malli
Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular metabolic settings with high resolution in real time. Our data indicate that mitochondria dynamically supply ATP for glucose phosphorylation in a variety of cancer cell types. This hexokinase-dependent process seems to be reversed upon the removal of glucose or other hexose sugars. Our data further verify that mitochondria in cancer cells have increased ATP consumption...
October 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/30303739/genes-controlling-the-activation-of-natural-killer-lymphocytes-are-epigenetically-remodeled-in-intestinal-cells-from-germ-free-mice
#19
Audrey Poupeau, Christian Garde, Karolina Sulek, Kiymet Citirikkaya, Jonas T Treebak, Manimozhiyan Arumugam, David Simar, Louise E Olofsson, Fredrik Bäckhed, Romain Barrès
Remodeling of the gut microbiota is implicated in various metabolic and inflammatory diseases of the gastrointestinal tract. We hypothesized that the gut microbiota affects the DNA methylation profile of intestinal epithelial cells (IECs) which could, in turn, alter intestinal function. In this study, we used mass spectrometry and methylated DNA capture to respectively investigate global and genome-wide DNA methylation of intestinal epithelial cells from germ-free (GF) and conventionally raised mice. In colonic IECs from GF mice, DNA was markedly hypermethylated...
October 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30303625/analysis-of-mitochondrial-dimensions-and-cristae-structure-in-pluripotent-stem-cells-using-transmission-electron-microscopy
#20
I C Tobias, R Khazaee, D H Betts
Dynamic alterations to mitochondrial structure and function regulate cell fate decisions and underlie multiple age-related and genetic diseases that are modeled using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Transmission electron microscopy (TEM) can be used to obtain high-resolution micrographs of mitochondria, but mitochondrial ultrastructure is easily distorted during specimen processing. This unit describes a method that preserves mitochondrial membrane structure from adherent ESC cultures for TEM sample preparation...
October 10, 2018: Current Protocols in Stem Cell Biology
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