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Focal adhesion kinase

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https://www.readbyqxmd.com/read/29333095/cinnamomum-cassia-extracts-suppress-human-lung-cancer-cells-invasion-by-reducing-u-pa-mmp-expression-through-the-fak-to-erk-pathways
#1
Hsing-Chen Wu, Chi-Ting Horng, You-Li Lee, Pei-Ni Chen, Chin-Yin Lin, Chen-Yu Liao, Yih-Shou Hsieh, Shu-Chen Chu
Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 μg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA)...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29332411/%C3%AE-1-integrin-mediated-multicellular-resistance-in-hepatocellular-carcinoma-through-activation-of-the-fak-akt-pathway
#2
Tao Tian, Chun-Li Li, Xiao Fu, Shu-Hong Wang, Jun Lu, Hui Guo, Yu Yao, Ke-Jun Nan, Yu-Juan Yang
Objective To explore the role and mechanism of β1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29328428/regulation-of-drug-resistance-and-metastasis-of-gastric-cancer-cells-via-the-microrna647-ank2-axis
#3
Wenlong Cao, Weiyuan Wei, Zexu Zhan, Dongyi Xie, Yubo Xie, Qiang Xiao
Due to a lack of effective methods for early diagnosis, the majority of patients with gastric cancer (GC) are diagnosed during the late stages of the disease, which are often accompanied by metastasis. For these patients, despite being considered an important therapeutic modality in the treatment of cancer, chemotherapy is usually not effective due to multidrug resistance (MDR). The expression levels of MDR/metastasis‑associated genes are regulated by numerous microRNAs (miRNAs/miRs). The expression of miR-647 in GC tissues and SGC7901/VCR cell line (drug resistance to vincristine) was detected by qRT-PCR...
January 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327067/overexpression-of-nogo-receptor-3-ngr3-correlates-with-poor-prognosis-and-contributes-to-the-migration-of-epithelial-cells-of-nasopharyngeal-carcinoma-patients
#4
Jiang-Yi He, Ping Han, Yu Zhang, Yong-Dong Liu, Shi-Jian Song, Guo-Kai Feng, Yu An, Ai-Jun Zhou, Hong-Bo Wang, Li Yuan, Zhi-Rui Lin, Tian-Liang Xia, Man-Zhi Li, Yan-Min Liu, Xiao-Ming Huang, Hua Zhang, Qian Zhong
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines...
January 11, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29322249/mir-375-inhibits-the-hepatocyte-growth-factor-elicited-migration-of-mesenchymal-stem-cells-by-downregulating-akt-signaling
#5
Lihong He, Xianyao Wang, Naixin Kang, Jianwei Xu, Nan Dai, Xiaojing Xu, Huanxiang Zhang
The migration of mesenchymal stem cells (MSCs) is critical for their use in cell-based therapies. Accumulating evidence suggests that microRNAs are important regulators of MSC migration. Here, we report that the expression of miR-375 was downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly stimulates the migration of these cells. Overexpression of miR-375 decreased the transfilter migration and the migration velocity of MSCs triggered by HGF. In our efforts to determine the mechanism by which miR-375 affects MSC migration, we found that miR-375 significantly inhibited the activation of Akt by downregulating its phosphorylation at T308 and S473, but had no effect on the activity of mitogen-activated protein kinases...
January 10, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29318780/the-synergistic-role-of-atp-dependent-drug-efflux-pump-and-focal-adhesion-signaling-pathways-in-vinorelbine-resistance-in-lung-cancer
#6
Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date
The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations...
January 10, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29317819/inhibition-of-cancer-cell-migration-with-cus-msio2-peg-nanoparticles-by-repressing-mmp-2-mmp-9-expression
#7
Guoying Deng, Feng Zhou, Zizheng Wu, Fei Zhang, Kerun Niu, Yingjie Kang, Xijian Liu, Qiugen Wang, Yin Wang, Qian Wang
The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29316327/physical-confinement-alters-cytoskeletal-contributions-towards-human-mesenchymal-stem-cell-migration
#8
Mary T Doolin, Kimberly M Stroka
The in vivo microenvironment is critical for providing physico-chemical signaling cues which ultimately regulate human mesenchymal stem cell (hMSC) behavior in clinically-relevant applications. hMSCs experience mechanical confinement of the cell body and nucleus in 3D tissues during homing and in porous tissue engineered scaffolds, yet the effects of this mechanical cue on hMSC migration are not known. Here, we use a microchannel device to systematically examine the effect of confinement on hMSC migration and cytoskeletal organization...
January 6, 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29314097/effect-of-fak-inhibitor-vs-6063-defactinib-on-docetaxel-efficacy-in-prostate-cancer
#9
Hui-Ming Lin, Brian Y Lee, Lesley Castillo, Calan Spielman, Judith Grogan, Nicole K Yeung, James G Kench, Phillip D Stricker, Anne-Maree Haynes, Margaret M Centenera, Lisa M Butler, S Martin Shreeve, Lisa G Horvath, Roger J Daly
BACKGROUND: Docetaxel, the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration-sensitive prostate cancer (CSPC) when combined with androgen-deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS-6063 on docetaxel efficacy in pre-clinical CRPC and CSPC models...
January 5, 2018: Prostate
https://www.readbyqxmd.com/read/29311227/src-and-confinement-dependent-fak-activation-causes-e-cadherin-relaxation-and-%C3%AE-catenin-activity
#10
Charlène Gayrard, Clément Bernaudin, Théophile Déjardin, Cynthia Seiler, Nicolas Borghi
In epithelia, E-cadherin cytoplasmic tail is under cytoskeleton-generated tension via a link that contains β-catenin. A cotranscription factor, β-catenin, is also active in morphogenetic processes associated with epithelial-to-mesenchymal transition. β-Catenin signaling appears mechanically inducible and was proposed to follow phosphorylation-induced β-catenin release from E-cadherin. Evidence for this mechanism is lacking, and whether E-cadherin tension is involved is unknown. To test this, we combined quantitative fluorescence microscopies with genetic and pharmacological perturbations of epithelial-to-mesenchymal transition-induced cells in culture...
January 8, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29306139/structure-of-focal-adhesion-kinase-in-healthy-heart-versus-pathological-cardiac-hypertrophy-a-modeling-and-simulation-study
#11
Pallavi Mohanty, Sonika Bhatnagar
Focal adhesion kinase (FAK) is required for signaling in the heart. S910 phosphorylated FAK is known to cause pathological cardiac hypertrophy. The switching of FAK between its inactive (-i), activated (-a) and hyperactive (-h) state is controlled by phosphorylation. FAK consists of three domains, namely: FERM, Kinase, and FAT joined by linkers L1 and L2. The structural basis of FAK phosphorylation and signaling to the downstream pathways is not understood. In this work, we carried out homology modeling and domain assembly of full length human iFAK and aFAK...
December 19, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29305421/fluid-flow-modulates-electrical-activity-in-cardiac-herg-potassium-channels
#12
Samrat Roy, M K Mathew
Fluid movement within the heart generates substantial shear forces, but the effect of this mechanical stress on the electrical activity of the human heart has not been examined. The fast component of the delayed rectifier potassium currents responsible for repolarization of the cardiac action potential, Ikr, is encoded by the hERG channel. Here, we exposed hERG1a channel-expressing HEK293T cells to laminar shear stress (LSS) and observed that this mechanical stress increased the whole-cell current by 30%-40%...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29303405/focal-adhesion-kinase-a-potential-therapeutic-target-for-pancreatic-cancer-and-malignant-pleural-mesothelioma
#13
Rajani Kanteti, Tamara Mirzapoiazova, Jacob J Riehm, Immanuel Dhanasingh, Bolot Mambetsariev, Jiale Wang, Prakash Kulkarni, Garima Kaushik, Parthasarathy Seshacharyulu, Moorthy P Ponnusamy, Hedy L Kindler, Mohd W Nasser, Surinder K Batra, Ravi Salgia
The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines...
January 5, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29298841/galectin-8-induces-partial-epithelial-mesenchymal-transition-with-invasive-tumorigenic-capabilities-involving-a-fak-egfr-proteasome-pathway-in-mdck-cells
#14
Claudia Oyanadel, Christopher Holmes, Evelyn Pardo, Claudio Retamal, Ronan Shaughnessy, Patricio Smith, Priscilla Cortes, Marcela Bravo-Zehnder, Claudia Metz, Teo Feuerhake, Diego Romero, Juan Carlos Roa, Viviana Montecinos, Andrea Soza, Alfonso González
Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal-transition (EMT). The glycan-binding protein Galectin-8 (Gal-8) is over-expressed by certain carcinomas and activates selective β1-integrins involved in EMT. Here we show that Gal-8 over-expression or exogenous addition promotes proliferation, migration and invasion in non-tumoral MDCK cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the EGFR, likely triggered by α5β1integrin binding...
January 3, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29295815/toxoplasma-gondii-disrupts-%C3%AE-1-integrin-signaling-and-focal-adhesion-formation-during-monocyte-hypermotility
#15
Joshua H Cook, Norikiyo Ueno, Melissa B Lodoen
The motility of blood monocytes is orchestrated by the activity of cell surface integrins, which translate extracellular signals into cytoskeletal changes to mediate adhesion and migration. Toxoplasma gondii is an intracellular parasite that infects migratory cells and enhances their motility, but the mechanisms underlying T. gondii-induced hypermotility are incompletely understood. We have investigated the molecular basis for the hypermotility of primary human peripheral blood monocytes and THP-1 cells infected with T...
January 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29286114/cigarette-smoke-induced-egfr-activation-promotes-epithelial-mesenchymal-migration-of-human-retinal-pigment-epithelial-cells-through-regulation-of-the-fak-mediated-syk-src-pathway
#16
Ga Bin Park, Daejin Kim
Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is inevitable change of age‑related macular degeneration (AMD). Smoking is a major risk factor for the development of EMT in several diseases, including lung cancer. Cigarette smoke‑induced stress promotes the production of epidermal growth factor (EGF) in RPE cells. However, the underlying signaling pathways induced by aberrant EGF receptor (EGFR) expression in cigarette smoke-exposed RPE cells remain largely unknown. In the present study, the morphological transformation and production of EMT-associated cytokines were investigated to analyze the effect of smoking on the retina...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29284478/phoyunnanin-e-inhibits-migration-of-non-small-cell-lung-cancer-cells-via-suppression-of-epithelial-to-mesenchymal-transition-and-integrin-%C3%AE-v-and-integrin-%C3%AE-3
#17
Nareerat Petpiroon, Boonchoo Sritularak, Pithi Chanvorachote
BACKGROUND: The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial-mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action. METHODS: The cytotoxic and proliferative effects of phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay...
December 29, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29282884/a-sticky-wicket-overexpression-of-integrin-alpha-11-is-sufficient-for-cardiac-fibrosis
#18
EDITORIAL
Andrew Leask
Increased mechanical loading in the microenvironment is linked to pathologies including fibrosis, a group of connective tissue disorders characterized by increased production of scar tissue that culminates in organ failure and, often, death. Cells sense surrounding stiffness via cell surface receptors called integrins, which stimulate downstream signaling molecules including focal adhesion kinase to cause further overproduction and remodeling of connective tissue. Thus increased mechanical loading (i.e., stiff connective tissue) perpetuates the fibrotic phenotype...
December 28, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29280977/flaccidoxide-13-acetate-extracted-from-the-soft-coral-cladiella-kashmani-reduces-human-bladder-cancer-cell-migration-and-invasion-through-reducing-activation-of-the-fak-pi3k-akt-mtor-signaling-pathway
#19
Choo-Aun Neoh, Wen-Tung Wu, Guo-Fong Dai, Jui-Hsin Su, Chih-I Liu, Tzu-Rong Su, Yu-Jen Wu
Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, urokinase-type plasminogen activator receptor (uPAR), focal adhesion kinase (FAK), phosphatidylinositide-3 kinases (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, Ras homolog gene family, member A (Rho A), Ras, mitogen-activated protein kinase kinase 7 (MKK7) and mitogen-activated protein kinase kinase kinase 3 (MEKK3), and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in RT4 and T24 cells...
December 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29260198/micro-and-nanoscale-topographies-on-silk-regulate-gene-expression-of-human-corneal-epithelial-cells
#20
Kai B Kang, Brian D Lawrence, X Raymond Gao, Yuncin Luo, Qiang Zhou, Aihong Liu, Victor H Guaiquil, Mark I Rosenblatt
Purpose: Corneal basement membrane has topographical features that provide biophysical cues to direct cell adherence, migration, and proliferation. In this study, we hypothesize that varying topographic pitch created on silk films can alter epithelial cell morphology, adhesion, and the genetic expression involved in cytoskeletal dynamics-related pathways. Methods: Silicon wafers with parallel ridge widths of 2000, 1000, and 800 nm were produced and used to pattern silk films via soft lithography...
December 1, 2017: Investigative Ophthalmology & Visual Science
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