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metabolism reprogramming

Tasleem Arif, Avijit Paul, Yakov Krelin, Anna Shteinfer-Kuzmine, Varda Shoshan-Barmatz
Oncogenic properties, along with the metabolic reprogramming necessary for tumour growth and motility, are acquired by cancer cells. Thus, tumour metabolism is becoming a target for cancer therapy. Here, cancer cell metabolism was tackled by silencing the expression of voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein that controls cell energy, as well as metabolic and survival pathways and that is often over-expressed in many cancers. We demonstrated that silencing VDAC1 expression using human-specific siRNA (si-hVDAC1) inhibited cancer cell growth, both in vitro and in mouse xenograft models of human glioblastoma (U-87MG), lung cancer (A549), and triple negative breast cancer (MDA-MB-231)...
December 8, 2018: Cancers
Marek M Nagiec, Jeremy R Duvall, Adam P Skepner, Eleanor A Howe, Jessica Bastien, Eamon Comer, Jean-Charles Marie, Stephen E Johnston, Joseph Negri, Michelle Eichhorn, Julien Vantourout, Clary Clish, Kiran Musunuru, Michael Foley, Jose R Perez, Michelle A J Palmer
Increased expression of the Tribbles pseudokinase 1 gene ( TRIB1 ) is associated with lower plasma levels of LDL cholesterol and triglycerides, higher levels of HDL cholesterol and decreased risk of coronary artery disease and myocardial infarction. We identified a class of tricyclic glycal core-based compounds that upregulate TRIB1 expression in human HepG2 cells and phenocopy the effects of genetic TRIB1 overexpression as they inhibit expression of triglyceride synthesis genes and ApoB secretion in cells...
November 1, 2018: MedChemComm
Jie Liu, Daniela Moyankova, Chih-Ta Lin, Petko Mladenov, Run-Ze Sun, Dimitar Djilianov, Xin Deng
BACKGROUND: Water shortage is a major factor that harms agriculture and ecosystems worldwide. Plants display various levels of tolerance to water deficit, but only resurrection plants can survive full desiccation of their vegetative tissues. Haberlea rhodopensis, an endemic plant of the Balkans, is one of the few resurrection plants found in Europe. We performed transcriptomic analyses of this species under slight, severe and full dehydration and recovery to investigate the dynamics of gene expression and associate them with existing physiological and metabolomics data...
December 13, 2018: BMC Plant Biology
Su Su, Anyonya R Guntur, Daniel C Nguyen, Shameem S Fakory, Chad C Doucette, Cassandra Leech, Humphrey Lotana, Matthew Kelley, Jaspreet Kohli, Julieta Martino, Sunder Sims-Lucas, Lucy Liaw, Calvin Vary, Clifford J Rosen, Aaron C Brown
Molecular- and cellular-based therapies have the potential to reduce obesity-associated disease. In response to cold, beige adipocytes form in subcutaneous white adipose tissue and convert energy stored in metabolic substrates to heat, making them an attractive therapeutic target. We developed a robust method to generate a renewable source of human beige adipocytes from induced pluripotent stem cells (iPSCs). Developmentally, these cells are derived from FOXF1+ mesoderm and progress through an expandable mural-like mesenchymal stem cell (MSC) to form mature beige adipocytes that display a thermogenically active profile...
December 11, 2018: Cell Reports
Luca Simula, Ilenia Pacella, Alessandra Colamatteo, Claudio Procaccini, Valeria Cancila, Matteo Bordi, Claudia Tregnago, Mauro Corrado, Martina Pigazzi, Vincenzo Barnaba, Claudio Tripodo, Giuseppe Matarese, Silvia Piconese, Silvia Campello
Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites...
December 11, 2018: Cell Reports
Åsa B Gustafsson, Gerald W Dorn
The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered as the mechanism primarily responsible for mitochondrial quality control. However, our understanding of how, why, and under what specific conditions mitophagy is activated has grown tremendously over the past decade...
January 1, 2019: Physiological Reviews
L Nájera, M Alonso-Juarranz, M Garrido, C Ballestín, L Moya, M Martínez-Díaz, R Carrillo, A Juarranz, F Rojo, J M Cuezva, J L Rodríguez-Peralto
BACKGROUND: Reprogramming of energy metabolism to enhanced aerobic glycolysis has been defined as a hallmark of cancer. OBJECTIVE: To investigate the role of the mitochondrial proteins, β-subunit of the H+ -ATP synthase (β-F1-ATPase), and heat-shock protein 60 (HSP60), and the glycolytic markers, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pyruvate kinase M2 (PKM2), as well as the bioenergetic cellular (BEC) index, in melanoma progression. MATERIAL AND METHODS: The expression of energy metabolism proteins were assessed on a set of different melanoma cells representing the natural biological history of the disease: primary cultures of melanocytes, radial (WM35) and vertical (WM278) growth phases, and poorly (C81-61-PA) and highly (C8161-HA) aggressive melanoma cells...
December 7, 2018: British Journal of Dermatology
You Dong Liu, Liang Yu, Le Ying, Jesse Balic, Hugh Gao, Nian Tao Deng, Alison West, Feng Yan, Cheng Bo Ji, Daniel Gough, Patrick Tan, Brendan J Jenkins, Ji Kun Li
Toll-like receptors (TLRs) play critical roles in host defence following recognition of conserved microbial- and host-derived components, and their dysregulation is a common feature of various inflammation-associated cancers, including gastric cancer (GC). Despite the recent recognition that metabolic reprogramming is a hallmark of cancer, the molecular effectors of altered metabolism during tumorigenesis remain unclear. Here, using bioenergetics function assays on human GC cells, we reveal that ligand-induced activation of TLR2, predominantly through TLR1/2 heterodimer, augments both oxidative phosphorylation (OXPHOS) and glycolysis, with a bias towards glycolytic activity...
December 11, 2018: International Journal of Cancer. Journal International du Cancer
V Krishnan Ramanujan
Cancer cells are known to display a variety of metabolic reprogramming strategies to fulfill their own growth and proliferative agenda. With the advent of high resolution imaging strategies, metabolomics techniques, and so forth, there is an increasing appreciation of critical role that tumor cell metabolism plays in the overall breast cancer (BC) growth. In this report, we demonstrate a sensitive, flow-cytometry-based assay for rapidly assessing the metabolic phenotypes in isolated suspensions of breast cancer cells...
December 11, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Susmita Mondal, Kaushik Bhattacharya, Chitra Mandal
The emergence and maintenance of cancer stem-like cells (CSCs) are usually governed by tumor niche. Tumor niche always provides metabolic challenges to cancer cells and CSCs mostly because of tissue hypoxia. However, the role of micro-environmental nutritional stress (NS) in dedifferentiation of cancer cells is poorly defined. Here, we developed a stochastic model of CSCs by gradual nutritional deprivation in glioblastoma multiforme (GBM) cells used as a model system. Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells (GSCs)-specific biomarkers with higher invasive and angiogenic properties...
2018: Cell Death Discovery
Jordan Rowlands, Julian Heng, Philip Newsholme, Rodrigo Carlessi
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions...
2018: Frontiers in Endocrinology
Kui Xie, Sherry Ngo, Jing Rong, Allan Sheppard
Lutein is a dietary carotenoid of particular nutritional interest as it is preferentially taken up by neural tissues. Often linked with beneficial effects on vision, a broader role for lutein in neuronal differentiation has emerged recently, although the underlying mechanisms for these effects are not yet clear. The purpose of this study was to investigate the effect of lutein on neuronal differentiation and explore the associated underpinning mechanisms. We found that lutein treatment enhanced the differentiation of SH-SY5Y cells, specifically increasing neuronal arborization and expression of the neuronal process filament protein microtubule-associated protein 2...
January 2019: Neural Regeneration Research
Noga Ron-Harel, Giulia Notarangelo, Jonathan M Ghergurovich, Joao A Paulo, Peter T Sage, Daniel Santos, F Kyle Satterstrom, Steven P Gygi, Joshua D Rabinowitz, Arlene H Sharpe, Marcia C Haigis
T cell-mediated immune responses are compromised in aged individuals, leading to increased morbidity and reduced response to vaccination. While cellular metabolism tightly regulates T cell activation and function, metabolic reprogramming in aged T cells has not been thoroughly studied. Here, we report a systematic analysis of metabolism during young versus aged naïve T cell activation. We observed a decrease in the number and activation of naïve T cells isolated from aged mice. While young T cells demonstrated robust mitochondrial biogenesis and respiration upon activation, aged T cells generated smaller mitochondria with lower respiratory capacity...
December 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Seitaro Nomura
Cardiomyopathy, a leading cause of death worldwide, is etiologically and phenotypically heterogeneous and is caused by a combination of genetic and non-genetic factors. Major genomic determinants of dilated cardiomyopathy (DCM) are titin truncating mutations and lamin A/C mutations. Patients with these two genotypes show critically different phenotypes, including penetrance, coexistence with a conduction system abnormality, cardiac prognosis, and treatment response. The transcriptomic and epigenomic characteristics of DCM include activation of the DNA damage response, metabolic reprogramming, and dedifferentiation...
December 4, 2018: Journal of Cardiology
Meilan He, Fan Cheng, Suzane Ramos da Silva, Brandon Tan, Océane Sorel, Marion Gruffaz, Tingting Li, Shou-Jiang Gao
Discovered in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) has been associated with four human malignancies including Kaposi's sarcoma, primary effusion lymphoma, a subset of multicentric Castleman's disease, and KSHV inflammatory cytokine syndrome. These malignancies mostly occur in immunocompromised patients including patients with acquired immunodeficiency syndrome and often cause significant mortality because of the lack of effective therapies. Significant progresses have been made to understand the molecular basis of KSHV infection and KSHV-induced oncogenesis in the last two decades...
2019: Cancer Treatment and Research
Hanyong Sun, Weiqin Yang, Yuan Tian, Xuezhen Zeng, Jingying Zhou, Myth T S Mok, Wenshu Tang, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, Yue-Sun Cheung, Paul B S Lai, Hector K S Wang, Shun-Wa Tsang, King-Lau Chow, Mengying Hu, Rihe Liu, Leaf Huang, Bing Yang, Pengyuan Yang, Ka-Fai To, Joseph J Y Sung, Grace L H Wong, Vincent W S Wong, Alfred S L Cheng
Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men, but the molecular mechanism remains obscure. Here, we show that an androgen receptor (AR)-driven oncogene, cell cycle-related kinase (CCRK), collaborates with obesity-induced pro-inflammatory signaling to promote non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Lentivirus-mediated Ccrk ablation in liver of male mice fed with high-fat high-carbohydrate diet abrogates not only obesity-associated lipid accumulation, glucose intolerance and insulin resistance, but also HCC development...
December 6, 2018: Nature Communications
Myung Jin Son, Jae Kap Jeong, Youjeong Kwon, Jae-Sung Ryu, Seon Ju Mun, Hye Jin Kim, Sung-Wuk Kim, Sanghee Yoo, Jiae Kook, Hongbum Lee, Janghwan Kim, Kyung-Sook Chung
Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process...
December 6, 2018: Experimental & Molecular Medicine
Daphne A C Stapels, Peter W S Hill, Alexander J Westermann, Robert A Fisher, Teresa L Thurston, Antoine-Emmanuel Saliba, Isabelle Blommestein, Jörg Vogel, Sophie Helaine
Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system...
December 7, 2018: Science
Julie Leca, Thorsten Berger, Tak Wah Mak
Metabolic reprogramming is a hallmark of cancer cell metabolism. Recently, in Cancer Cell, Ye and colleagues (2018) reported that leukemic cells have the capacity to modulate glucose metabolism in multiple organs of their host, thereby increasing the glucose resources available for malignant cell growth.
December 4, 2018: Cell Metabolism
Wei Xu, Jonathan D Powell
Signaling and transcriptional regulation of metabolic reprogramming upon T cell activation has been studied intensively. In this issue of Cell Metabolism, Ricciardi et al. (2018) show that translational regulation of key metabolic enzymes GLUT1 and ACC1 plays a novel role in human naive CD4 T cell activation and subset differentiation.
December 4, 2018: Cell Metabolism
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