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Focal adhesion kinase

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https://www.readbyqxmd.com/read/29786754/regulation-of-interferon-signaling-and-hcv%C3%A2-rna-replication-by-extracellular-matrix
#1
Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki
Although interferon (IFN)‑based treatment of patients with chronic hepatitis C virus (HCV) infection is widely applied, treatment resistance is often observed in patients with advanced liver fibrosis. Given that the molecular mechanisms of IFN resistance in liver fibrosis remain elusive, the present study investigated the effects of extracellular matrix (ECM) on IFN signaling in hepatic cells. The native HuH‑7 human hepatoma cell line and HuH‑7 cells were stably transfected with full‑length HCV‑RNA fused with Renilla luciferase (OR6 cells) were cultured on ECM‑coated dishes or non‑coated plastic dishes (NDs), and treated with human IFN‑α...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786069/ve-cadherin-promotes-vasculogenic-mimicry-by-modulating-kaiso-dependent-gene-expression
#2
Daniel Delgado-Bellido, Mónica Fernández-Cortés, María Isabel Rodríguez, Santiago Serrano-Sáenz, Arkaitz Carracedo, Angel Garcia-Diaz, F Javier Oliver
Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29784011/extremely-low-frequency-electromagnetic-fields-promote-mesenchymal-stem-cell-migration-by-increasing-intracellular-ca-2-and-activating-the-fak-rho-gtpases-signaling-pathways-in-vitro
#3
Yingchi Zhang, Jiyuan Yan, Haoran Xu, Yong Yang, Wenkai Li, Hua Wu, Chaoxu Liu
BACKGROUND: The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. METHODS: We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29782321/pyk2-is-a-novel-tau-tyrosine-kinase-that-is-regulated-by-the-tyrosine-kinase-fyn
#4
Chuanzhou Li, Jürgen Götz
The protein tyrosine kinase Pyk2 is encoded by PTK2B, a novel Alzheimer's disease (AD) susceptibility variant, with the PTK2B risk allele being associated with increased mRNA levels, suggestive of increased Pyk2 levels. However, the role of Pyk2, a member of the focal adhesion kinase (FAK) family, in AD pathology and its regulation are largely unknown. To address this, we generated mice with neuronal expression of human Pyk2. Because we had previously reported an association of Pyk2 and hyperphosphorylated tau (a hallmark feature of AD) in human tau transgenic pR5 mice, we also generated Pyk2/tau double-transgenic mice, which exhibit increased tyrosine phosphorylation and accumulation of tau...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29777737/type-i-collagen-induces-mesenchymal-cell-differentiation-into-myofibroblasts-through-yap-induced-tgf-%C3%AE-1-activation
#5
Xiaoling Liu, Xinyu Long, Weiwei Liu, Yeli Zhao, Toshihiko Hayashi, Masayuki Yamato, Kazunori Mizuno, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takaaki Ogura, Yuji Atsuzawa, Takashi Ikejima
In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive...
May 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29777374/the-tenascin-c-derived-peptide-vswrapta-promotes-neuronal-branching-via-transcellular-activation-of-the-focal-adhesion-kinase-fak-and-the-erk1-2-signaling-pathway-in-vitro
#6
Marvin Jarocki, Omar Sallouh, Ralf Weberskirch, Andreas Faissner
The central nervous system (CNS) of mammals has a limited regeneration capacity after traumatic events, which causes chronic functional disability. The development of biomaterials aims at providing support for the regeneration process. One strategy integrates peptides that mimic functional domains of extracellular matrix (ECM) or cell adhesion molecules with synthetic polymers designed to present growth-supporting cues to the neuronal microenvironment. Thus, small peptide sequences originating from molecules of the ECM may serve as promising bio-additives, acting as artificial matricryptins to gear cellular processes...
May 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29775632/controlled-delivery-of-a-focal-adhesion-kinase-inhibitor-results-in-accelerated-wound-closure-with-decreased-scar-formation
#7
Kun Ma, Sun Hyung Kwon, Jagannath Padmanabhan, Dominik Duscher, Artem A Trotsyuk, Yixiao Dong, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C Gurtner
Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries...
May 15, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#8
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29763784/alterations-in-the-distribution-of-actin-and-its-binding-proteins-in-the-porcine-endometrium-during-early-pregnancy-possible-role-in-epithelial-remodeling-and-embryo-adhesion
#9
Beenu Moza Jalali, Pawel Likszo, Aneta Andronowska, Dariusz J Skarzynski
During early pregnancy, uterine epithelial cells undergo major transformations in their cytoskeleton that make the endometrium receptive for conceptus attachment. Actin binding proteins (ABPs) such as cofilin, gelsolin, and vinculin are involved in regulating actin polymerization, severing or crosslinking actin to integrins. However, whether ABPs are involved in epithelial remodeling or embryo adhesion in pigs is unknown. Therefore, the expression and distribution of these proteins were investigated in porcine endometrium on Days 10 and 13 (pre-implantation period), and 16 (attachment phase) of the estrous cycle or pregnancy...
May 8, 2018: Theriogenology
https://www.readbyqxmd.com/read/29763414/cd93-promotes-integrin-%C3%AE-1-activation-and-fibronectin-fibrillogenesis-during-tumor-angiogenesis
#10
Roberta Lugano, Kalyani Vemuri, Di Yu, Michael Bergqvist, Anja Smits, Magnus Essand, Staffan Johansson, Elisabetta Dejana, Anna Dimberg
Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation...
May 15, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29758283/tgf-%C3%AE-fibronectin-and-integrin-%C3%AE-5%C3%AE-1-promote-invasion-in-basal-cell-carcinoma
#11
François Kuonen, Isabelle Surbeck, Kavita Y Sarin, Monique Dontenwill, Curzio Ruegg, Michel Gilliet, Anthony E Oro, Olivier Gaide
Basal cell carcinoma (BCC) is the most frequent human cancer and is becoming an important health problem in an ageing population. Based on their clinical and histological characteristics, thick BCC are typically divided into low-risk nodular and high-risk infiltrative subtypes, although the underlying mechanisms are poorly understood. We have identified molecular mechanisms that explain the aggressiveness of high-risk infiltrative BCC, with a potential direct clinical impact. In this study, we first show that fibroblasts, TGFβ and fibronectin are found preferentially in infiltrative human BCC...
May 11, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29749547/salidroside-inhibits-the-proliferation-and-migration-of-gastric-cancer-cells-via-suppression-of-src%C3%A2-associated-signaling-pathway-activation-and-heat-shock-protein-70-expression
#12
Zhilin Qi, Tuo Tang, Lili Sheng, Yunfei Ma, Yinhua Liu, Liang Yan, Shimei Qi, Liefeng Ling, Yao Zhang
Salidroside, an active ingredient extracted from the Rhodiola rosea plant, has potential anti‑tumor effects. However, the effects of salidroside on gastric cancer cell proliferation and migration remain unclear. In the present study, the inhibitory effects of salidroside on gastric cancer cell proliferation, migration and invasion and the molecular mechanisms underlying these effects were investigated. The human gastric cancer cell line, BGC‑823, was treated with different concentrations of salidroside (200, 400 and 600 µg/ml)...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749523/overexpression-of-annexin-a1-protects-against-benzo-a-pyrene%C3%A2-induced-bronchial-epithelium-injury
#13
Yanfei Cui, Shengya Yang
The incidence of asthma is increasing worldwide. Bronchial epithelium injury is common in asthma. The regulatory role of Annexin A1 (ANXA1) in bronchial epithelium injury is currently not well understood. The aim of the present study was to evaluate the role of ANXA1 on bronchial epithelium injury. The cell viability and levels of apoptosis were respectively tested by Cell Counting Kit‑8 and flow cytometry. Reactive oxygen species (ROS) content and the activity of oxidative indicators were assessed by commercial kits...
May 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29747634/regulation-of-fibroblast-fas-expression-by-soluble-and-mechanical-pro-fibrotic-stimuli
#14
Amos E Dodi, Iyabode O Ajayi, Christine Chang, Meghan Beard, Shanna L Ashley, Steven K Huang, Victor J Thannickal, Daniel J Tschumperlin, Thomas H Sisson, Jeffrey C Horowitz
BACKGROUND: Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when Fas (CD95) expression is increased in these cells. Moreover, prior work shows that Fas expression in fibrotic lung fibroblasts is reduced by epigenetic silencing of the Fas promoter...
May 10, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29746877/liraglutide-attenuates-the-migration-of-retinal-pericytes-induced-by-advanced-glycation-end-products
#15
Wen-Jian Lin, Xue-Fei Ma, Ming Hao, Huan-Ran Zhou, Xin-Yang Yu, Ning Shao, Xin-Yuan Gao, Hong-Yu Kuang
Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability...
May 7, 2018: Peptides
https://www.readbyqxmd.com/read/29740048/matrilysin-mmp-7-cleavage-of-perlecan-hspg2-complexed-with-semaphorin-3a-supports-fak-mediated-stromal-invasion-by-prostate-cancer-cells
#16
Brian J Grindel, Jerahme R Martinez, Tristen V Tellman, Daniel A Harrington, Hamim Zafar, Luay Nakhleh, Leland W Chung, Mary C Farach-Carson
Interrupting the interplay between cancer cells and extracellular matrix (ECM) is a strategy to halt tumor progression and stromal invasion. Perlecan/heparan sulfate proteoglycan 2 (HSPG2) is an extracellular proteoglycan that orchestrates tumor angiogenesis, proliferation, differentiation and invasion. Metastatic prostate cancer (PCa) cells degrade perlecan-rich tissue borders to reach bone, including the basement membrane, vasculature, reactive stromal matrix and bone marrow. Domain IV-3, perlecan's last 7 immunoglobulin repeats, mimics native proteoglycan by promoting tumoroid formation...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29738483/proline-rich-protein-tyrosine-kinase-2-in-inflammation-and-cancer
#17
REVIEW
Xiangdong Zhu, Yonghua Bao, Yongchen Guo, Wancai Yang
Focal adhesion kinase (FAK) and its homologous FAK-related proline-rich tyrosine kinase 2 (Pyk2) contain the same domain, exhibit high sequence homology and are defined as a distinct family of non-receptor tyrosine kinases. This group of kinases plays critical roles in cytoskeletal dynamics and cell adhesion by regulating survival and growth signaling. This review summarizes the physiological and pathological functions of Pyk2 in inflammation and cancers. In particular, overexpression of Pyk2 in cancerous tissues is correlated with poor outcomes...
May 8, 2018: Cancers
https://www.readbyqxmd.com/read/29737477/cyclic-tensile-strain-upregulates-pro-inflammatory-cytokine-expression-via-fak-mapk-signaling-in-chondrocytes
#18
Makoto Yanoshita, Naoto Hirose, Yuki Okamoto, Chikako Sumi, Mami Takano, Sayuri Nishiyama, Yuki Asakawa-Tanne, Kayo Horie, Azusa Onishi, Yuka Yamauchi, Tomomi Mitsuyoshi, Ryo Kunimatsu, Kotaro Tanimoto
Excessive mechanical stimulation is considered an important factor in the destruction of chondrocytes. Focal adhesion kinase (FAK) is non-receptor tyrosine kinase related to a number of different signaling proteins. Little is known about the function of FAK in chondrocytes under mechanical stimulation. In the present study, we investigated the function of FAK in mechanical signal transduction and the mechanism through which cyclic tensile strain (CTS) induces expression of inflammation-related factors. Mouse ATDC5 chondrogenic cells were subjected to CTS of 0...
May 8, 2018: Inflammation
https://www.readbyqxmd.com/read/29736312/focal-adhesion-kinase-fak-deficiency-in-mononuclear-phagocytes-alters-murine-breast-tumor-progression
#19
Ryan A Llewellyn, Michael F Gutknecht, Keena S Thomas, Mark R Conaway, Amy H Bouton
While it has long been recognized that mononuclear phagocytes play a significant role in determining breast tumor progression, the molecular factors that contribute to these events are not fully understood. In this report, we sought to determine whether focal adhesion kinase (FAK) expression in this cell population influences primary breast tumor initiation and growth. Using the MMTV-polyoma middle T (PyVmT) murine model of spontaneous breast cancer, we found that FAK expression in mononuclear phagocytes accelerates tumor initiation/progression during the early stages of PyVmT tumor growth but subsequently restricts tumor growth once the tumors have transitioned to malignancy...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29734338/rit1-controls-actin-dynamics-via-complex-formation-with-rac1-cdc42-and-pak1
#20
Uta Meyer Zum Büschenfelde, Laura Isabel Brandenstein, Leonie von Elsner, Kristina Flato, Tess Holling, Martin Zenker, Georg Rosenberger, Kerstin Kutsche
RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1...
May 2018: PLoS Genetics
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