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Metabolic reprogramming

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https://www.readbyqxmd.com/read/29222329/glutaminolysis-is-required-for-tgf-%C3%AE-1-induced-myofibroblast-differentiation-and-activation
#1
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis.  Myofibroblast differentiation is characterized by the expression of alpha-smooth muscle actin (α-SMA) and extracellular matrix (ECM) proteins, and is dependent on metabolic reprogramming.  In this study, we explored the role of glutaminolysis and metabolites of the tricarboxylic acid cycle (TCA) in supporting myofibroblast differentiation.  Glutaminolysis converts glutamine (Gln) into alpha-ketoglutarate (α-KG), a critical intermediate in the TCA cycle...
December 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29221154/expression-of-ganglioside-gd2-reprogram-the-lipid-metabolism-and-emt-phenotype-in-bladder-cancer
#2
Venkatrao Vantaku, Sri Ramya Donepudi, Chandrashekar R Ambati, Feng Jin, Vasanta Putluri, Khoa Nguyen, Kimal Rajapakshe, Cristian Coarfa, Venkata Lokesh Battula, Yair Lotan, Nagireddy Putluri
High-grade Bladder Cancer (BLCA) represents the most aggressive and treatment-resistant cancer that renders the patients with poor survival. However, only a few biomarkers have been identified for the detection and treatment of BLCA. Recent studies show that ganglioside GD2 can be used as cancer biomarker and/or therapeutic target for various cancers. Despite its potential relevance in cancer diagnosis and therapeutics, the role of GD2 is unknown in BLCA. Here, we report for the first time that high-grade BLCA tissues and cell lines have higher expression of GD2 compared to low-grade by high-resolution Mass Spectrometry...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216217/the-emerging-role-of-asc-in-dendritic-cell-metabolism-during-chlamydia-infection
#3
Danielle N McKeithen, Yusuf O Omosun, Khamia Ryans, Jing Mu, Zhonglin Xie, Tankya Simoneaux, Uriel Blas-Machado, Francis O Eko, Carolyn M Black, Joseph U Igietseme, Qing He
Chlamydia trachomatis is a bacterial agent that causes sexually transmitted infections worldwide. The regulatory functions of dendritic cells (DCs) play a major role in protective immunity against Chlamydia infections. Here, we investigated the role of ASC in DCs metabolism and the regulation of DCs activation and function during Chlamydia infection. Following Chlamydia stimulation, maturation and antigen presenting functions were impaired in ASC-/- DCs compared to wild type (WT) DCs, in addition, ASC deficiency induced a tolerant phenotype in Chlamydia stimulated DCs...
2017: PloS One
https://www.readbyqxmd.com/read/29215097/the-molecular-dialogue-between-arabidopsis-thaliana-and-the-necrotrophic-fungus-botrytis-cinerea-leads-to-major-changes-in-host-carbon-metabolism
#4
Florian Veillet, Cécile Gaillard, Pauline Lemonnier, Pierre Coutos-Thévenot, Sylvain La Camera
Photoassimilates play crucial roles during plant-pathogen interactions, as colonizing pathogens rely on the supply of sugars from hosts. The competition for sugar acquisition at the plant-pathogen interface involves different strategies from both partners which are critical for the outcome of the interaction. Here, we dissect individual mechanisms of sugar uptake during the interaction of Arabidopsis thaliana with the necrotrophic fungus Botrytis cinerea using millicell culture insert, that enables molecular communication without physical contact...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29213317/dynamic-changes-in-transcriptome-and-cell-wall-composition-underlying-brassinosteroid-mediated-lignification-of-switchgrass-suspension-cells
#5
Xiaolan Rao, Hui Shen, Sivakumar Pattathil, Michael G Hahn, Ivana Gelineo-Albersheim, Debra Mohnen, Yunqiao Pu, Arthur J Ragauskas, Xin Chen, Fang Chen, Richard A Dixon
Background: Plant cell walls contribute the majority of plant biomass that can be used to produce transportation fuels. However, the complexity and variability in composition and structure of cell walls, particularly the presence of lignin, negatively impacts their deconstruction for bioenergy. Metabolic and genetic changes associated with secondary wall development in the biofuel crop switchgrass (Panicum virgatum) have yet to be reported. Results: Our previous studies have established a cell suspension system for switchgrass, in which cell wall lignification can be induced by application of brassinolide (BL)...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29212894/hiv-and-cardiovascular-disease-role-of-immunometabolic-perturbations
#6
REVIEW
Eman Teer, M Faadiel Essop
The successful rollout of anti-retroviral therapy ensured that HIV is increasingly managed as a chronic condition. HIV-positive persons are therefore exhibiting increased cardiovascular complications. This review focuses on the emerging role of "immunometabolism" within the context of HIV-related immune dysregulation and cardiovascular disease onset. Here, persistent immune activation contributes to pathophysiological perturbations during early infection, resulting in immune cell metabolic reprogramming and the activation of coagulation pathways in HIV-positive individuals...
January 1, 2018: Physiology
https://www.readbyqxmd.com/read/29212308/metabolic-signaling-to-epigenetic-alterations-in-cancer
#7
REVIEW
Jung-Ae Kim, Young Il Yeom
Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212306/oncogene-driven-metabolic-alterations-in-cancer
#8
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/29212304/the-pentose-phosphate-pathway-as-a-potential-target-for-cancer-therapy
#9
REVIEW
Eunae Sandra Cho, Yong Hoon Cha, Hyun Sil Kim, Nam Hee Kim, Jong In Yook
During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#10
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212182/oncogenic-p95her2-611ctf-primes-human-breast-epithelial-cells-for-metabolic-stress-induced-down-regulation-of-flip-and-activation-of-trail-r-caspase-8-dependent-apoptosis
#11
Rosa Martín-Pérez, Rosario Yerbes, Rocío Mora-Molina, Ana Cano-González, Joaquín Arribas, Massimiliano Mazzone, Abelardo López-Rivas, Carmen Palacios
Oncogenic transformation triggers reprogramming of cell metabolism, as part of the tumorigenic process. However, metabolic reprogramming may also increase the sensitivity of transformed cells to microenvironmental stress, at the early stages of tumor development. Herein, we show that transformation of human breast epithelial cells by the p95HER2/611CTF oncogene markedly sensitizes these cells to metabolic stress induced by the simultaneous inhibition of glucose and glutamine metabolism. In p95HER2/611CTF-transformed cells, metabolic stress activates a TNF related apoptosis-inducing ligand (TRAIL)-R and caspase-8-dependent apoptotic process that requires prior down-regulation of cellular FLICE-like inhibitor protein (c-FLIP) levels...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210650/reprograming-carcinoma-associated-fibroblasts-by-micrornas
#12
Y Xu, X Zhou, M Mei, Y Ren
Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during development of several cancer types, and therefore emerge as an attractive therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the functions of CAFs have already been in clinical trials. However, these drugs exhibit limited efficacy in patients, partially due to the fact that currently used biomarkers for determining efficacy are not CAF-specific. Furthermore, depletion of CAFs may promote carcinogenesis and accelerate cancer progression by inducing immunosuppression and hypoxia, leading to reduced survival...
December 4, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29209641/the-folate-cycle-is-a-new-metabolic-weakness-of-cancer
#13
Derek Lee, Carmen Chak-Lui Wong
Cancer cells harness nutrients to support its rapid proliferation through metabolic reprogramming. Our report identified folate cycle as a metabolic target in hepatocellular carcinoma. Folate cycle stagnation via inhibition of its mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) greatly induced oxidative stress improving HCC cells' response to sorafenib.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29208970/integrated-mrna-and-microrna-transcriptome-analysis-reveals-mirna-regulation-in-response-to-pva-in-potato
#14
Yanlin Li, Xinxi Hu, Jiren Chen, Wanxing Wang, Xingyao Xiong, Changzheng He
Potato (Solanum tuberosum L.) is the fourth most important crop worldwide. Potato virus A (PVA) is one of the most harmful viruses infecting potatoes. However, the molecular mechanisms governing the responses to PVA infection in potato at the transcriptional and post-transcriptional levels are not well understood. In this study, we performed both mRNA and small RNA sequencing in potato leaves to identify the genes and miRNAs involved in the response to PVA infection. A total of 2,062 differentially expressed genes (DEGs) and 201 miRNAs (DEMs) were identified, respectively...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29208682/the-receptor-tyrosine-kinase-epha2-promotes-glutamine-metabolism-in-tumors-by-activating-the-transcriptional-coactivators-yap-and-taz
#15
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/29207533/molecular-and-genetic-determinants-of-glioma-cell-invasion
#16
REVIEW
Kenta Masui, Yoichiro Kato, Tatsuo Sawada, Paul S Mischel, Noriyuki Shibata
A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, "diffuse glioma", which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity...
December 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29207313/regulation-of-host-pathogen-interactions-via-the-post-transcriptional-csr-rsm-system
#17
REVIEW
Maria Kusmierek, Petra Dersch
A successful colonization of specific hosts requires a rapid and efficient adaptation of the virulence-relevant gene expression program by bacterial pathogens. An important element in this endeavor is the Csr/Rsm system. This multi-component, post-transcriptional control system forms a central hub within complex regulatory networks and coordinately adjusts virulence properties with metabolic and physiological attributes of the pathogen. A key function is elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous target mRNAs, many of which encode crucial virulence factors, and alters their translation, stability or elongation of transcription...
December 2, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29207019/stromal-epithelial-lactate-shuttle-induced-by-tumor%C3%A2-derived-interleukin%C3%A2-1%C3%AE-promotes-cell-proliferation-in-oral-squamous-cell-carcinoma
#18
Jie Wu, Yun Hong, Tong Wu, Juan Wang, Xiaobing Chen, Zhi Wang, Bin Cheng, Juan Xia
Stromal-epithelial lactate shuttle is an essential process to support fast‑growing tumor cells, however, the underlying mechanism remains ambiguous. Interleukin‑1β (IL‑1β), which is a key node gene in both stromal and epithelial cells of oral squamous cell carcinoma (OSCC), may participate in this metabolic reprogramming. In the present study, anaerobic glycolysis of cancer‑associated fibroblasts (CAFs) was evaluated and the role of IL‑1β in regulating stromal‑epithelial lactate shuttle was determined...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29205357/hexokinase-2-dependent-hyperglycolysis-driving-microglial-activation-contributes-to-ischemic-brain-injury
#19
Yuan Li, Bingzheng Lu, Longxiang Sheng, Zhu Zhu, Hongjiaqi Sun, Yuwei Zhou, Yang Yang, Dongdong Xue, Wenli Chen, Xuyan Tian, Yun Du, Min Yan, Wenbo Zhu, Fan Xing, Kai Li, Suizhen Lin, Pengxin Qiu, Xingwen Su, Yijun Huang, Guangmei Yan, Wei Yin
Hyperglycolysis, observed within the penumbra zone during brain ischemia, was shown to be detrimental for tissue survival due to lactate accumulation and reactive oxygen species (ROS) overproduction in clinical and experimental settings. Recently, mounting evidence suggests that glycolytic reprogramming and induced metabolic enzymes can fuel the activation of peripheral immune cells. However, the possible roles and details regarding hyperglycolysis in neuroinflammation during ischemia are relatively poorly understood...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29204835/oral-cancer-stem-cells-microenvironment
#20
Prajna Paramita Naik, Prashanta Kumar Panda, Sujit K Bhutia
Cancer stem cells (CSCs) play important role in tumor growth and metastasis coupled with increased recurrences and acquired therapeutic resistance in oral cancer. The tumor microenvironment imposes intense pressure in cancer evolution in response to adverse growth conditions, resource limitation and immune predation. Here, we discussed the dynamic interplay between cancer stem cells and tumor microenvironment in the formation of intratumoral heterogeneity to modulate tumor progression. The CSCs niche provide a special microhabitat for survival, maintenance of stemness and tumor re-propagation...
2017: Advances in Experimental Medicine and Biology
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