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https://www.readbyqxmd.com/read/27919568/all-trans-retinoic-acid-suppresses-the-adhering-ability-of-arpe-19-cells-via-mitogen-activated-protein-kinase-and-focal-adhesion-kinase
#1
Yo-Chen Chang, Yuh-Shin Chang, Ming-Chu Hsieh, Horng-Jiun Wu, Meng-Hsien Wu, Chia-Wei Lin, Wen-Chuan Wu, Ying-Hsien Kao
This study investigated the signaling mechanism underlying the anti-adhesive effect of all-trans retinoic acid (ATRA) on retinal pigment epithelial ARPE-19 cells. Adhesion kinetics with or without ATRA treatment were profiled by adhesion assay. Surface coating with type IV collagen, fibronectin, laminin, but not type I collagen, significantly enhanced adhesion and spreading of ARPE-19 cells, while ATRA at subtoxic doses (ranging from 10(-7) to 10(-6) M) profoundly suppressed the extracellular matrix-enhanced adhesion ability...
November 16, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27918830/the-antiangiogenic-effects-of-gold-nanoparticles-on-experimental-choroidal-neovascularization-in-mice
#2
Young-Jung Roh, Chang Rae Rho, Won-Kyung Cho, Seungbum Kang
Purpose: The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice. Methods: Choroidal neovascularization was induced by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27913654/novel-small-molecule-jp-153-targets-the-src-fak-paxillin-signaling-complex-to-inhibit-vegf-induced-retinal-angiogenesis
#3
Jordan J Toutounchian, Jayaprakash Pagadala, Duane D Miller, Jerome Baudry, Frank Park, Edward Chaum, Charles R Yates
Targeting vascular endothelial growth factor (VEGF) is a common treatment strategy for neovascular eye disease, a major cause of vision loss in diabetic retinopathy and age-related macular degeneration. However, the decline in clinical efficacy over time in many patients suggests that monotherapy of anti-VEGF protein therapeutics may benefit from adjunctive treatments. Our previous work has shown that through decreased activation of the cytoskeletal protein paxillin, growth factor-induced ischemic retinopathy in the murine oxygen-induced retinopathy model could be inhibited...
January 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/27911269/the-matricellular-protein-cyr61-promotes-breast-cancer-lung-metastasis-by-facilitating-tumor-cell-extravasation-and-suppressing-anoikis
#4
Yu-Ting Huang, Qiang Lan, Girieca Lorusso, Nathalie Duffey, Curzio Rüegg
Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909410/mechanosensitive-molecular-networks-involved-in-transducing-resistance-exercise-signals-into-muscle-protein-accretion
#5
REVIEW
Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27905395/outside-in-integrin-signalling-regulates-haematopoietic-stem-cell-function-via-periostin-itgav-axis
#6
Satish Khurana, Sarah Schouteden, Javed K Manesia, Albert Santamaria-Martínez, Joerg Huelsken, Adam Lacy-Hulbert, Catherine M Verfaillie
Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates HSC proliferation. Systemic deletion of Postn results in peripheral blood (PB) anaemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. Postn(-/-) mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn(-/-) mice show accumulation of DNA damage generally associated with aged HSCs...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signalling-and-platelet-function-through-upregulation-of-protein-kinase-a-activity
#7
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis...
November 29, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27895123/addressing-the-functional-determinants-of-fak-during-ciliogenesis-in-multiciliated-cells
#8
Ioanna Antoniades, Panayiota Stylianou, Neophytos Christodoulou, Paris A Skourides
We have previously identified FAK as an important regulator of ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins associate with the basal bodies and their striated rootlets and form complexes named ciliary adhesions (CAs). CAs display similarities with FAs but are established in an integrin independent fashion and are responsible for anchoring basal bodies to the actin cytoskeleton during ciliogenesis, as well as in mature multiciliated cells. FAK downregulation leads to aberrant ciliogenesis due to impaired association between the basal bodies and the actin cytoskeleton, suggesting that FAK is an important regulator of the CA complex...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27893827/astrocyte-structural-and-molecular-response-to-elevated-intraocular-pressure-occurs-rapidly-and-precedes-axonal-tubulin-rearrangement-within-the-optic-nerve-head-in-a-rat-model
#9
Shandiz Tehrani, Lauren Davis, William O Cepurna, Tiffany E Choe, Diana C Lozano, Ashley Monfared, Lauren Cooper, Joshua Cheng, Elaine C Johnson, John C Morrison
Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir...
2016: PloS One
https://www.readbyqxmd.com/read/27893716/hic-5-remodeling-of-the-stromal-matrix-promotes-breast-tumor-progression
#10
G J Goreczny, J L Ouderkirk-Pecone, E C Olson, M Krendel, C E Turner
The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5(-/-) mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5(-/-);PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5(+/-);PyMT mice...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27890644/epithelial-membrane-protein-2-and-%C3%AE-1-integrin-signaling-regulate-apc-mediated-processes
#11
Alyssa C Lesko, Jenifer R Prosperi
Adenomatous Polyposis Coli (APC) plays a critical role in cell motility, maintenance of apical-basal polarity, and epithelial morphogenesis. We previously demonstrated that APC loss in Madin Darby Canine Kidney (MDCK) cells increases cyst size and inverts polarity independent of Wnt signaling, and upregulates the tetraspan protein, Epithelial Membrane Protein 2 (EMP2). Herein, we show that APC loss increases β1 integrin expression and migration of MDCK cells. Through 3D in vitro model systems and 2D migration analysis, we have depicted the molecular mechanism(s) by which APC influences polarity and cell motility...
November 24, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27882385/a-role-for-neuregulin-1-in-promoting-keloid-fibroblast-migration-via-erbb2-mediated-signaling
#12
Natalie Jumper, Tom Hodgkinson, Ralf Paus, Ardeshir Bayat
Keloid disease is a fibroproliferative tumour characterised by aggressive local invasion, evident from a clinically and histologically active migrating margin. During combined laser capture microdissection and microarray analysis-based in situ gene expression profiling, we identified upregulation of the polypeptide growth factor neuregulin-1 (NRG1) and ErbB2 oncogene in keloid margin dermis, leading to the hypothesis that NRG1 contributed to keloid margin migration through ErbB2-mediated signalling. The aim of this study was to probe this hypothesis through functional in vitro studies...
November 24, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27881487/osteogenesis-requires-fak-dependent-collagen-synthesis-by-fibroblasts-and-osteoblasts
#13
Dhaarmini Rajshankar, Yongqiang Wang, Christopher A McCulloch
Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6 kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked, shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced bone volume (4-fold in tails; P < 0...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27876318/selectivity-switch-between-fak-and-pyk2-macrocyclization-of-fak-inhibitors-improves-pyk2-potency
#14
Julie Farand, Nicholas Mai, Jayaraman Chandrasekhar, Zachary E Newby, Josh Van Veldhuizen, Jennifer Loyer-Drew, Chandrasekar Venkataramani, Juan Guerrero, Amy Kwok, Ning Li, Yelena Zherebina, Sibylle Wilbert, Jeff Zablocki, Gary Phillips, William J Watkins, Robert Mourey, Gregory T Notte
Herein, we describe the synthesis of Pyk2 inhibitors via macrocyclization of FAK and dual Pyk2-FAK inhibitors. We identified macrocycle 25a as a highly potent Pyk2 inhibitor (IC50=0.7nM), with ∼175-fold improvement in Pyk2 potency as compared to its acyclic counterpart. In many cases, macrocyclization improved Pyk2 potency while weakening FAK potency, thereby improving the Pyk2/FAK selectivity ratio for this structural class of inhibitors. Various macrocyclic linkers were studied in an attempt to optimize Pyk2 selectivity...
December 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27868012/ptk2-fak-a-new-predictive-biomarker-for-response-to-radiotherapy-in-head-and-neck-squamous-cell-carcinoma
#15
COMMENT
Emma J de Ruiter, Stefan M Willems
No abstract text is available yet for this article.
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27865925/orai1-and-orai2-mediate-store-operated-calcium-entry-that-regulates-hl60-cell-migration-and-fak-phosphorylation
#16
R Diez-Bello, I Jardin, G M Salido, J A Rosado
Store-operated Ca(2+) entry (SOCE) is a major mechanism for the regulation of intracellular Ca(2+) homeostasis and cellular function. Emerging evidence has revealed that altered expression and function of the molecular determinants of SOCE play a critical role in the development or maintenance of several cancer hallmarks, including enhanced proliferation and migration. Here we show that, in the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the transcript level, followed by the expression of Orai1...
November 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in-b-progenitor-acute-lymphoblastic-leukemia
#17
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27865045/high-krt8-expression-promotes-tumor-progression-and-metastasis-of-gastric-cancer
#18
Fang Jian, Wang Hao, Liu Yun, Ding Fangfang, Ni Ying, Shao Shihe
Keratin8 (KRT8) is the major component of the intermediate filament cytoskeleton and predominantly expressed in simple epithelial tissues. Aberrant expression of KRT8 is associated with multiple tumor progression and metastasis. However, the role of KRT8 in Gastric Cancer (GC) remains unclear. In this study, KRT8 expression was investigated and it was found to be up-regulated along with human GC progression and metastasis at both mRNA and protein levels in human gastric cancer tissues. In addition, KRT8 over expression enhanced the proliferation and migration of human gastric cancer cells, whereas the knock-down of KRT8 by siRNA only inhibited migration of human gastric cancer cells...
November 17, 2016: Cancer Science
https://www.readbyqxmd.com/read/27863391/nordihydroguaiaretic-acid-impairs-prostate-cancer-cell-migration-and-tumor-metastasis-by-suppressing-neuropilin-1
#19
Xin Li, Shengjun Fan, Xueyang Pan, Yilixiati Xiaokaiti, Jianhui Duan, Yundi Shi, Yan Pan, Lu Tie, Xin Wang, Yuhua Li, Xuejun Li
Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27856458/focal-adhesion-kinase-promotes-the-progression-of-aortic-aneurysm-by-modulating-macrophage-behavior
#20
Takasuke Harada, Koichi Yoshimura, Osamu Yamashita, Koshiro Ueda, Noriyasu Morikage, Yasuhiro Sawada, Kimikazu Hamano
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear. APPROACH AND RESULTS: We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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