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https://www.readbyqxmd.com/read/27936345/targeting-integrin-linked-kinase-to-suppress-oncogenic-kras-signaling-in-pancreatic-cancer
#1
Po-Chen Chu, Samuel K Kulp, Tanios Bekaii-Saab, Ching-Shih Chen
Although oncogenic KRAS represents a therapeutically relevant target in pancreatic cancer, it is deemed "non-druggable" because of the intrinsic difficulty in designing direct inhibitors of KRAS. Our recent work demonstrated a KRAS-integrin-linked kinase (ILK) regulatory feedback loop that allows pancreatic cancer cells to regulate KRAS expression and to interact with the tumor microenvironment to promote aggressive phenotype. KRAS induces E2F1-mediated transcriptional activation of ILK expression, and ILK, in turn, controls KRAS expression via hnRNPA1, which binds and destabilizes the G-quadruplex in the KRAS promoter...
December 9, 2016: Small GTPases
https://www.readbyqxmd.com/read/27934087/a-multifunctional-platform-for-tumor-angiogenesis-targeted-chemo-thermal-therapy-using-polydopamine-coated-gold-nanorods
#2
Lu Zhang, Huilan Su, Jiali Cai, Dengfeng Cheng, Yongjie Ma, Jianping Zhang, Chuanqing Zhou, Shiyuan Liu, Hongcheng Shi, Yingjian Zhang, Chunfu Zhang
Image-guided combined chemo-thermal therapy assists in optimizing treatment time, enhancing therapeutic efficiency, and circumventing side effects. In the present study, we developed a chemo-photothermal theranostic platform based on polydopamine (PDA)-coated gold nanorods (GNRs). The PDA coating was thin; however, it significantly suppressed the cytotoxicity of the cetyltrimethylammonium bromide template and allowed high cisplatin loading efficiency, arginine-glycine-aspartic acid (RGD) peptide (c(RGDyC)) conjugation, and chelator-free iodine-125 labeling (RGD-(125)IPt-PDA@GNRs)...
November 22, 2016: ACS Nano
https://www.readbyqxmd.com/read/27933817/peptide-mediated-platelet-capture-at-gold-micropore-arrays
#3
Kellie Adamson, Elaine Spain, Una Prendergast, Niamh Moran, Robert J Forster, Tia E Keyes
Ordered spherical cap gold cavity arrays with 5.4, 1.6, and 0.98 μm diameter apertures were explored as capture surfaces for human blood platelets to investigate the impact of surface geometry and chemical modification on platelet capture efficiency and their potential as platforms for surface enhanced Raman spectroscopy of single platelets. The substrates were chemically modified with single-constituent self-assembled monolayers (SAM) or mixed SAMs comprised of thiol-functionalized arginine-glycine-aspartic acid (RGD, a platelet integrin target) with or without 1-octanethiol (adhesion inhibitor)...
November 30, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27933619/monocyte-mediated-activation-of-endothelial-cells-occurs-only-after-binding-to-extracellular-vesicles-from-red-blood-cell-products-a-process-mediated-by-%C3%AE-integrin
#4
Marleen Straat, Maike E van Hezel, Anita Böing, Anita Tuip-De Boer, Nina Weber, Rienk Nieuwland, Robin van Bruggen, Nicole P Juffermans
BACKGROUND: Red blood cell (RBC) transfusion is associated with organ failure. The mechanism remains unknown, but may include adherence of blood cells to the microvasculature. We hypothesized that RBC-derived extracellular vesicles (EVs) interact with monocytes to activate endothelial cells. STUDY DESIGN AND METHODS: Human umbilical vein endothelial cells were incubated with supernatant from fresh and stored RBC units either containing EVs or depleted from EVs, with or without the addition of immune cells...
December 2016: Transfusion
https://www.readbyqxmd.com/read/27933404/genome-wide-high-content-sirna-screening-identifies-the-alzheimer-s-genetic-risk-factor-fermt2-as-a-major-modulator-of-app-metabolism
#5
Julien Chapuis, Amandine Flaig, Benjamin Grenier-Boley, Fanny Eysert, Virginie Pottiez, Gaspard Deloison, Alexandre Vandeputte, Anne-Marie Ayral, Tiago Mendes, Shruti Desai, Alison M Goate, John S K Kauwe, Florence Leroux, Adrien Herledan, Florie Demiautte, Charlotte Bauer, Fréderic Checler, Ronald C Petersen, Kaj Blennow, Henrik Zetterberg, Lennart Minthon, Vivianna M Van Deerlin, Virginia Man-Yee Lee, Leslie M Shaw, John Q Trojanowski, Marilyn Albert, Abhay Moghekar, Richard O'Brien, Elaine R Peskind, Nicolas Malmanche, Gerard D Schellenberg, Pierre Dourlen, Ok-Ryul Song, Carlos Cruchaga, Philippe Amouyel, Benoit Deprez, Priscille Brodin, Jean-Charles Lambert
Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer's disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the "post-GWAS" era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism...
December 8, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#6
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27932295/the-interconnections-between-autophagy-and-integrin-mediated-cell-adhesion
#7
REVIEW
Ariadne Vlahakis, Jayanta Debnath
Autophagy is a cellular degradation process integral for promoting cellular adaptation during metabolic stress while also functioning as a cellular homeostatic mechanism. Mounting evidence also demonstrates that autophagy is induced upon loss of integrin-mediated cell attachments to the surrounding extracellular matrix (ECM). Analogous to its established cytoprotective role during nutrient starvation, autophagy protects cells from detachment-induced cell death, termed anoikis. Here, we review the significance of autophagy as an anoikis resistance pathway, focusing on the intracellular signals associated with integrins that modulate the autophagy response and dictate the balance between cell death and survival following loss of cell-matrix contact...
December 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27931795/ikk%C3%AE-inibition-by-a-glucosamine-derivative-enhances-maspin-expression-in-osteosarcoma-cell-line
#8
Martina Leopizzi, Rossana Cocchiola, Edoardo Milanetti, Domenico Raimondo, Laura Politi, Cesare Giordano, Roberto Scandurra, Anna Scotto d'Abusco
Chronic inflammation has been associated to cancer development by the alteration of several inflammatory pathways, such as Nuclear Factor-κB pathway. In particular, IκB kinase α (IKKα), one of two catalytic subunit of IKK complex, has been described to be associated to cancer progression and metastasis in a number of cancers. The molecular mechanism by which IKKα affects cancer progression is not yet completely clarified, anyway an association between IKKα and the expression of Maspin (Mammary Serine Protease Inhibitor or SerpinB5), a tumor suppressor protein, has been described...
December 5, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27931517/glut1-promotes-cell-proliferation-migration-and-invasion-by-regulating-epidermal-growth-factor-receptor-and-integrin-signaling-in-triple-negative-breast-cancer-cells
#9
Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/MAPK signaling pathway and integrin β1/Src/FAK signaling pathways...
December 9, 2016: BMB Reports
https://www.readbyqxmd.com/read/27931516/expansion-of-hair-follicle-stem-cells-sticking-to-isolated-sebaceous-glands-to-generate-in-vivo-epidermal-structures
#10
Huishan Zhang, Huashan Zhao, Jingqiao Qiao, Shoubing Zhang, Shuang Liu, Na Li, Xiaohua Lei, Lina Ning, Yujing Cao, Enkui Duan
Hair follicle stem cells (HFSCs) are considered one of the useful donor cell types for skin regenerative medicine owing to their robust proliferative capacity and multipotency. However, methods for easily and effectively obtaining HFSCs from a limited skin biopsy are still lacking. Here we report a novel approach for obtaining a subpopulation of HFSCs from a small skin sample from the rat tail, which uses the sebaceous glands (SGs) to capture the adjacent HFSCs. By means of organ culture, keratinocytes were expanded from the detached SGs, which also included adherent HFSCs from the hair follicle that could be passaged at the single-cell level...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27931240/skeletal-muscle-characteristics-are-preserved-in-htert-cdk4-human-myogenic-cell-lines
#11
Matthew Thorley, Stéphanie Duguez, Emilia Maria Cristina Mazza, Sara Valsoni, Anne Bigot, Kamel Mamchaoui, Brennan Harmon, Thomas Voit, Vincent Mouly, William Duddy
BACKGROUND: hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically pertinent models of various neuromuscular disorders and in numerous fundamental studies of muscle cell function. However, the cell cycle is linked to other cellular processes such as integrin regulation, the PI3K/Akt pathway, and microtubule stability, raising the question as to whether genetic modification related to the cell cycle results in secondary effects that could undermine the validity of these cell models...
December 8, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27931025/ulcerative-colitis
#12
Elena Sonnenberg, Britta Siegmund
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is chronically present in patients throughout their lives. Hence, the chronic nature of the disease invariably requires continuous medical treatment. Advances in medical therapy over the last decades and current developments offer increasing options and are closely associated with a better life quality in patients. SUMMARY: Recent developments in understanding the pathogenesis of UC are discussed...
December 9, 2016: Digestion
https://www.readbyqxmd.com/read/27930828/integrin-and-cadherin-clusters-a-robust-way-to-organize-adhesions-for-cell-mechanics
#13
Rishita Changede, Michael Sheetz
Recent studies at the nanometer scale have revealed that relatively uniform clusters of adhesion proteins (50-100 nm) constitute the modular units of cell adhesion sites in both cell-matrix and cell-cell adhesions. Super resolution microscopy and membrane protein diffusion studies both suggest that even large focal adhesions are formed of 100 nm clusters that are loosely aggregated. Clusters of 20-50 adhesion molecules (integrins or cadherins) can support large forces through avidity binding interactions but can also be disassembled or endocytosed rapidly...
December 8, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27930408/vedolizumab-as-induction-and-maintenance-therapy-for-crohn-s-disease-in-patients-na%C3%A3-ve-to-or-who-have-failed-tumor-necrosis-factor-antagonist-therapy
#14
Bruce E Sands, William J Sandborn, Gert Van Assche, Milan Lukas, Jing Xu, Alexandra James, Brihad Abhyankar, Karen Lasch
BACKGROUND: Vedolizumab is a gut-selective α4β7 integrin antagonist for the treatment of moderately to severely active Crohn's disease (CD). Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha (TNF-α) antagonist therapy (TNF-naïve) or who had discontinued TNF-α antagonist therapy because of inadequate response (i.e., primary nonresponse), loss of response, or intolerance (collectively classified as the TNF-failure population)...
December 7, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27930308/epithelial-self-healing-is-recapitulated-by-a-3d-biomimetic-e-cadherin-junction
#15
Daniel J Cohen, Martijn Gloerich, W James Nelson
Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell-cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apical-basal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherin-mediated cell-cell adhesions on the orthogonal, lateral surfaces between cells...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929432/integrins-in-the-spotlight-of-cancer
#16
REVIEW
Daniela Bianconi, Matthias Unseld, Gerald W Prager
Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27929375/implications-of-the-differing-roles-of-the-%C3%AE-1-and-%C3%AE-3-transmembrane-and-cytosplasmic-domains-for-integrin-function
#17
Zhenwei Lu, Sijo Mathew, Jiang Chen, Arina Hadziselimovic, Riya Palamuttam, Billy G Hudson, Reinhard Faessler, Ambra Pozzi, Charles R Sanders, Roy Zent
Integrins are transmembrane receptors composed of α and β subunits. Although most integrins contain β1, canonical activation mechanisms are based on studies of the platelet integrin, αIIbβ3. Its inactive conformation is characterized by association of the αIIb transmembrane and cytosolic domain (TM/CT) with a tilted β3 TM/CT that leads to activation when disrupted. We show significant structural differences between β1 and β3 TM/CT in bicelles. Moreover, the 'snorkeling' lysine at the TM/CT interface of β subunits, previously proposed to regulate αIIbβ3 activation by ion pairing with nearby lipids, plays opposite roles in β1 and β3 integrin function and in neither case is responsible for TM tilt...
December 8, 2016: ELife
https://www.readbyqxmd.com/read/27928505/collagen-a-network-for-regenerative-medicine
#18
REVIEW
K M Pawelec, S M Best, R E Cameron
The basic building block of the extra-cellular matrix in native tissue is collagen. As a structural protein, collagen has an inherent biocompatibility making it an ideal material for regenerative medicine. Cellular response, mediated by integrins, is dictated by the structure and chemistry of the collagen fibers. Fiber formation, via fibrillogenesis, can be controlled in vitro by several factors: pH, ionic strength, and collagen structure. After formation, fibers are stabilized via cross-linking. The final bioactivity of collagen scaffolds is a result of both processes...
October 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/27927968/%C3%AE-%C3%AE-t-cells-coexpressing-gut-homing-%C3%AE-4%C3%AE-7-and-%C3%AE-e-integrins-define-a-novel-subset-promoting-intestinal-inflammation
#19
Jeong-Su Do, Sohee Kim, Karen Keslar, Eunjung Jang, Emina Huang, Robert L Fairchild, Theresa T Pizarro, Booki Min
γδ T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. In this study, we identified a unique γδ T cell subset that coexpresses high levels of gut-homing integrins, CD103 and α4β7. They were exclusively found in the mesenteric lymph node after T cell-mediated colitis induction, and their appearance preceded the inflammation. Adoptive transfer of the CD103(+)α4β7(high) subsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27927700/cardiac-%C3%AE-v%C3%AE-3-integrin-expression-following-acute-myocardial-infarction-in-humans
#20
William S A Jenkins, Alex T Vesey, Colin Stirrat, Martin Connell, Christophe Lucatelli, Anoushka Neale, Catriona Moles, Anna Vickers, Alison Fletcher, Tania Pawade, Ian Wilson, James H F Rudd, Edwin J R van Beek, Saeed Mirsadraee, Marc R Dweck, David E Newby
OBJECTIVE: Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI. METHODS: (18)F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1)...
December 7, 2016: Heart: Official Journal of the British Cardiac Society
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