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https://www.readbyqxmd.com/read/28819582/relationship-of-metabolic-alterations-and-pd-l1-expression-in-cisplatin-resistant-lung-cancer
#1
M Wangpaichitr, H Kandemir, Y Y Li, C Wu, Djm Nguyen, L G Feun, M T Kuo, N Savaraj
Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose...
April 28, 2017: Cell & Developmental Biology
https://www.readbyqxmd.com/read/28776197/long-term-exposure-of-immortalized-keratinocytes-to-arsenic-induces-emt-impairs-differentiation-in-organotypic-skin-models-and-mimics-aspects-of-human-skin-derangements
#2
R Weinmuellner, K Kryeziu, B Zbiral, K Tav, B Schoenhacker-Alte, D Groza, L Wimmer, M Schosserer, F Nagelreiter, S Rösinger, M Mildner, E Tschachler, M Grusch, J Grillari, P Heffeter
Arsenic is one of the most important human carcinogens and environmental pollutants. However, the evaluation of the underlying carcinogenic mechanisms is challenging due to the lack of suitable in vivo and in vitro models, as distinct interspecies differences in arsenic metabolism exist. Thus, it is of high interest to develop new experimental models of arsenic-induced skin tumorigenesis in humans. Consequently, aim of this study was to establish an advanced 3D model for the investigation of arsenic-induced skin derangements, namely skin equivalents, built from immortalized human keratinocytes (NHEK/SVTERT3-5)...
August 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28774727/reprogramming-to-developmental-plasticity-in-cancer-stem-cells
#3
REVIEW
Caitlin O'Brien-Ball, Adrian Biddle
During development and throughout adult life, sub-populations of cells exist that exhibit phenotypic plasticity - the ability to differentiate into multiple lineages. This behaviour is important in embryogenesis, is exhibited in a more limited context by adult stem cells, and can be re-activated in cancer cells to drive important processes underlying tumour progression. A well-studied mechanism of phenotypic plasticity is the epithelial-to-mesenchymal transition (EMT), a process which has been observed in both normal and cancerous cells...
July 31, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28774348/epithelial-to-mesenchymal-transition-in-fhc-silenced-cells-the-role-of-cxcr4-cxcl12-axis
#4
I Aversa, F Zolea, C Ieranò, S Bulotta, A M Trotta, M C Faniello, C De Marco, D Malanga, F Biamonte, G Viglietto, G Cuda, S Scala, F Costanzo
BACKGROUND: Ferritin plays a central role in the intracellular iron metabolism; the molecule is a nanocage of 24 subunits of the heavy and light types. The heavy subunit (FHC) is provided of a ferroxidase activity and thus performs the key transformation of iron in a non-toxic form. Recently, it has been shown that FHC is also involved in additional not iron-related critical pathways including, among the others, p53 regulation, modulation of oncomiRNAs expression and chemokine signalling...
August 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28745316/elevation-of-adenylate-energy-charge-by-angiopoietin-like-4-enhances-epithelial-mesenchymal-transition-by-inducing-14-3-3%C3%AE-expression
#5
Z Teo, M K Sng, J S K Chan, M M K Lim, Y Li, L Li, T Phua, J Y H Lee, Z W Tan, P Zhu, N S Tan
Metastatic cancer cells acquire energy-intensive processes including increased invasiveness and chemoresistance. However, how the energy demand is met and the molecular drivers that coordinate an increase in cellular metabolic activity to drive epithelial-mesenchymal transition (EMT), the first step of metastasis, remain unclear. Using different in vitro and in vivo EMT models with clinical patient's samples, we showed that EMT is an energy-demanding process fueled by glucose metabolism-derived adenosine triphosphate (ATP)...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28724942/physiological-oxygen-tension-reduces-hepatocyte-dedifferentiation-in-in-vitro-culture
#6
Ren Guo, Xinxiu Xu, Yuting Lu, Xin Xie
Primary hepatocytes cultured in vitro are a powerful tool to study the functions of hepatocytes and to evaluate the metabolism and toxicity of new drugs. However, in vitro culture of hepatocytes has proven to be very difficult. Ordinary culture conditions lead to dedifferentiation of hepatocytes, resulting in rapid change in cell morphology and significant reduction in specific cell functions. In the current study, we show that hepatocyte dedifferentiation is a rapid process under 21% O2 conditions. Hepatocytes cultured in 21% O2 undergo epithelial-to-mesenchymal transition (EMT), obtain fibroblast-like morphology, and show decreased hepatic functions...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722313/cellular-glycosylation-senses-metabolic-changes-and-modulates-cell-plasticity-during-emt
#7
REVIEW
P Carvalho-Cruz, F Alisson-Silva, A R Todeschini, W B Dias
Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward Hexosamine Biosynthesis Pathway (HBP) which fuels aberrant glycosylation patterns that are extensively observed in cancer cells...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-codelivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#8
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 31, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#9
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28683815/metabolic-labeling-in-middle-down-proteomics-allows-for-investigation-of-the-dynamics-of-the-histone-code
#10
Simone Sidoli, Congcong Lu, Mariel Coradin, Xiaoshi Wang, Kelly R Karch, Chrystian Ruminowicz, Benjamin A Garcia
BACKGROUND: Middle-down mass spectrometry (MS), i.e., analysis of long (~50-60 aa) polypeptides, has become the method with the highest throughput and accuracy for the characterization of combinatorial histone posttranslational modifications (PTMs). The discovery of histone readers with multiple domains, and overall the cross talk of PTMs that decorate histone proteins, has revealed that histone marks have synergistic roles in modulating enzyme recruitment and subsequent chromatin activities...
July 6, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28681242/the-potential-role-of-platelets-in-the-consensus-molecular-subtypes-of-colorectal-cancer
#11
REVIEW
Michael Lam, Jason Roszik, Preeti Kanikarla-Marie, Jennifer S Davis, Jeffrey Morris, Scott Kopetz, David G Menter
The consensus molecular subtypes (CMS) in colorectal cancer (CRC) represent distinct molecular subcategories of disease as reflected by comprehensive molecular profiling. The four CMS subtypes represent unique biology. CMS1 represents high immune infiltration. CMS2 demonstrates upregulation of canonical pathways such as WNT signaling. Widespread metabolic changes are seen in CMS3. CMS4 represents a mesenchymal phenotype with hallmark features including complement activation, matrix remodeling, angiogenesis, epithelial-mesechymal transition (EMT), integrin upregulation and stromal infiltration...
July 6, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28675930/proteomic-analysis-of-the-e3-ubiquitin-ligase-hakai-highlights-a-role-in-plasticity-of-the-cytoskeleton-dynamics-and-in-the-proteasome-system
#12
Andrea Díaz-Díaz, Alba Casas-Pais, Valentina Calamia, Raquel Castosa, Olaia Martinez-Iglesias, Daniel Roca-Lema, Isabel Santamarina, Manuel Valladares-Ayerbes, Lourdes Calvo, Venancio Chantada, Angélica Figueroa
Carcinoma, the most common type of cancer, arises from epithelial cells. The transition from adenoma to carcinoma is associated with the loss of E-cadherin and, in consequence, the disruption of cell-cell contacts. E-cadherin is a tumor suppressor, and it is down-regulated during epithelial-to-mesenchymal transition (EMT); indeed, its loss is a predictor of poor prognosis. Hakai is an E3 ubiquitin-ligase protein that mediates E-cadherin ubiquitination, endocytosis and finally degradation, leading the alterations of cell-cell contacts...
July 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28649002/cpla2%C3%AE-activates-pi3k-akt-and-inhibits-smad2-3-during-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells
#13
Hui Fu, Yuchao He, Lisha Qi, Lu Chen, Yi Luo, Liwei Chen, Yongmei Li, Ning Zhang, Hua Guo
Cytosolic phospholipase A2α (cPLA2α), a key phospholipase that regulates lipid metabolism, plays an important role in tumor progression. In the present study of hepatocellular carcinoma (HCC), cPLA2α was overexpressed in highly metastatic HCC cell lines. Immunohistochemical staining showed increased levels of cPLA2α at the invasive edges of HCC, and a clinicopathological analysis of samples from 111 patients revealed that its expression level was linked with micro-vascular invasion and cirrhosis. Knockdown of cPLA2α inhibited migration, probably due to its role in actin polymerization...
June 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28640191/phenotypic-plasticity-and-cell-fate-decisions-in-cancer-insights-from-dynamical-systems-theory
#14
REVIEW
Dongya Jia, Mohit Kumar Jolly, Prakash Kulkarni, Herbert Levine
Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes...
June 22, 2017: Cancers
https://www.readbyqxmd.com/read/28634226/phostine-pst3-1a-targets-mgat5-and-inhibits-glioblastoma-initiating-cell-invasiveness-and-proliferation
#15
Zahra Hassani, Ali Saleh, Soumaya Turpault, Salim Khiati, Willy Morelle, Jacques Vignon, Jean-Philippe Hugnot, Emmanuelle Uro-Coste, Philippe Legrand, Marcel Delaforge, Séverine Loiseau, Ludovic Clarion, Marc Lecouvey, Jean-Noël Volle, David Virieux, Jean-Luc Pirat, Hugues Duffau, Norbert Bakalara
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-Hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell based assays it is demonstrated that PST3...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28629038/electrospinning-of-pva-sericin-nanofiber-and-the-effect-on-epithelial-mesenchymal-transition-of-a549-cells
#16
Shanshan Yan, Xiuchun Li, Jing Dai, Yiqun Wang, Binbin Wang, Yi Lu, Jianlin Shi, Pengyu Huang, Jinkang Gong, Yuan Yao
This research aims to investigate the cell-nanomaterial interaction between epithelial-mesenchymal transition of A549 cell and electrospinning nanofibers composed of polyvinyl alcohol (PVA)/silk sericin (SS). The electrospinning of regenerated nanofiber was performed with water as a spinning solvent and glutaraldehyde as a chemical cross-linker. Solution concentration, applied voltage and spin distances as well as other parameters were optimized to generate fine nanofibers with smooth surface in good homogeneity...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28623323/rufy3-interaction-with-foxk1-promotes-invasion-and-metastasis-in-colorectal-cancer
#17
Ruyi Xie, Jing Wang, Xuehua Liu, Liqing Wu, Hui Zhang, Weimei Tang, Yueqiao Li, Li Xiang, Ying Peng, Xiaoting Huang, Yang Bai, Guangnan Liu, Aimin Li, Yadong Wang, Ye Chen, Yuexin Ren, Guoxin Li, Wei Gong, Side Liu, Jide Wang
RUFY3 is highly expressed in brain tissue and has a role in neuronal development. Transcriptional factor FOXK1 is involved in cell growth and metabolism. We knew that RUFY3 or FOXK1 has been correlated with the malignant of tumor cells. However, the role of these molecules in colorectal cancer (CRC) progression remains unknown. We investigated the protein expression levels by Western blot, immunofluorescence and immunohistochemistry analyses. The migration and invasive abilities of CRC cells were assessed using shRNA-mediated inhibition in vitro and in vivo...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602165/aberrant-cancer-metabolism-in-epithelial-mesenchymal-transition-and-cancer-metastasis-mechanisms-in-cancer-progression
#18
REVIEW
Run Huang, Xiangyun Zong
Cancer metastasis is a prominent feature of cancer cells, which is responsible for most cancer -associated mortality. Epithelial-mesenchymal transition (EMT) plays an essential role in the initiation and development of cancer metastasis. Studies have shown that EMT can induce cancer metastasis by promoting tumor malignances, reprograming cancer metabolism, and disrupting extracellular matrix. Accumulating evidence has demonstrated that aberrant cancer metabolism can induce EMT through multiple pathological pathways...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28599074/beyond-epithelial-to-mesenchymal-transition-common-suppression-of-differentiation-programs-underlies-epithelial-barrier-dysfunction-in-mild-moderate-and-severe-asthma
#19
Lucas F Loffredo, Hiam Abdala-Valencia, Kishore R Anekalla, Lyda Cuervo-Pardo, Cara J Gottardi, Sergejs Berdnikovs
BACKGROUND: Epithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood. METHODS: We used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes...
June 9, 2017: Allergy
https://www.readbyqxmd.com/read/28595943/a-role-for-g-protein-coupled-estrogen-receptor-gper-in-estrogen-induced-carcinogenesis-dysregulated-glandular-homeostasis-survival-and-metastasis
#20
REVIEW
Edward J Filardo
Mechanisms of carcinogenesis by estrogen center on its mitogenic and genotoxic potential on tumor target cells. These models suggest that estrogen receptor (ER) signaling promotes expansion of the transformed population and that subsequent accumulation of somatic mutations that drive cancer progression occur via metabolic activation of cathecol estrogens or by epigenetic mechanisms. Recent findings that GPER is linked to obesity, vascular pathology and immunosuppression, key events in the development of metabolic syndrome and intra-tissular estrogen synthesis, provides an alternate view of estrogen-induced carcinogenesis...
June 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
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