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Focal adhesion kinase

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https://www.readbyqxmd.com/read/28729346/distinct-pka-regulatory-subunits-mediate-pge2-inhibition-of-tgf%C3%AE-1-stimulated-collagen-i-translation-and-myofibroblast-differentiation
#1
Scott H Wettlaufer, L Raghu Penke, Katsuhide Okunishi, Marc Peters-Golden
Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Here we examined the role of specific PKAR subunit isoforms in these inhibitory actions in transforming growth factorβ-1 (TGFβ-1)-stimulated human lung fibroblasts (HLFs)...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28726546/nanotopographic-influence-on-the-in-vitro-behavior-of-induced-pluripotent-stem-cells
#2
Ji-Yun Ko, Hyun-Jik Oh, Jimin Lee, Gun-Il Im
While the influence of nanotopography on stem cell behavior have been extensively investigated on adult stem cells, far fewer studies have investigated the interaction of induced pluripotent stem cells (iPSC) with various nanotopographical patterns. The purpose of this study was to identify nanopatterns that can influence the stemness and proliferation as well as the adhesive properties in iPSCs, and thereby explore the feasibility of applying these nano-features for regenerative medicine. Three kinds of nanopatterns were fabricated from polydimethylsiloxane (PDMS) membranes, irregular patterned membrane (IPM), groove patterned membrane (GPM), and post patterned membrane (PPM), in addition to flat patterned membrane (FPM) which did not have any nanotopographic features and was used as the control pattern...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28723623/daurinol-blocks-breast-and-lung-cancer-metastasis-and-development-by-inhibition-of-focal-adhesion-kinase-fak
#3
Jong K Woo, Hyun J Jung, Ji-Youn Park, Ju-Hee Kang, Byung I Lee, DongYun Shin, Chu W Nho, Soo-Young Cho, Je K Seong, Seung H Oh
FAK overexpression has been reported in diverse primary and metastatic tumor tissues, supporting its pro-tumorigenic and pro-metastatic roles. Therefore, we have developed a neo-treatment strategy using daurinol to effectively treat cancer metastasis. Daurinol blocked cancer cell migration and invasion in vitro and exhibited anti-metastatic activity in an experimental metastasis model of breast and lung cancer. Daurinol selectively inhibited phosphorylation of FAK at Tyr925, Tyr576/577, and Tyr397 sites in a dose- and time-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718435/agrin-to-yap-in-cancer-and-neuromuscular-junctions
#4
Wen-Cheng Xiong, Lin Mei
Agrin is utilized by motor neurons to stimulate the LRP4-MuSK receptor in muscles for neuromuscular junction (NMJ) formation. Recent studies of cancer have identified novel functions of the low-density lipoprotein receptor-related protein 4-muscle-specific kinase (LRP4-MuSK) pathway. Agrin may act as a mechanotransduction signal in the extracellular matrix (ECM) to coordinate the cross-talk between the LRP4-MuSK pathway and integrin-focal adhesion pathway. Ensuing Yes-associated protein (YAP) activation promotes hepatocellular carcinoma (HCC)...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#5
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28713929/microrna-379-inhibits-metastasis-and-epithelial-mesenchymal-transition-via-targeting-fak-akt-signaling-in-gastric-cancer
#6
Meizhong Xu, Shui Qin, Fan Cao, Shi Ding, Mengnan Li
Accumulating evidence demonstrates that aberrant miRNAs contribute to gastric cancer (GC) development and progression. However, the roles of various miRNAs in GC remain to be determined. In the present study, we confirmed that a reduced miR-379 expression was present in GC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-379 expression was significantly correlated with poor prognostic features including lymph node metastasis and advanced TNM stage. Moreover, we confirmed that miR-379 was a novel independent prognostic marker for predicting 5-year survival of GC patients...
July 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#7
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28703800/killing-two-birds-with-one-stone-dual-blockade-of-integrin-and-fgf-signaling-through-targeting-syndecan-4-in-postoperative-capsular-opacification
#8
Yingyan Qin, Yi Zhu, Furong Luo, Chuan Chen, Xiaoyun Chen, Mingxing Wu
The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proliferation and migration of LECs to the posterior capsule lead to the development of PCO. Cell adhesion is mainly mediated by the binding of integrin to extracellular matrix proteins, while cell proliferation and migration are regulated by fibroblast growth factor (FGF)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28701377/microrna-206-modulates-an-rtn4a-cxcr4a-thbs3a-axis-in-newly-forming-somites-to-maintain-and-stabilize-the-somite-boundary-formation-of-zebrafish-embryos
#9
Cheng-Yung Lin, Jun-Yu He, Chih-Wei Zeng, Moo-Rumg Loo, Wen-Yen Chang, Po-Hsiang Zhang, Huai-Jen Tsai
Although microRNA-206 (miR-206) is known to regulate proliferation and differentiation of muscle fibroblasts, the role of miR-206 in early-stage somite development is still unknown. During somitogenesis of zebrafish embryos, reticulon4a (rtn4a) is specifically repressed by miR-206. The somite boundary was defective, and actin filaments were crossing over the boundary in either miR-206-knockdown or rtn4a-overexpressed embryos. In these treated embryos, C-X-C motif chemokine receptor 4a (cxcr4a) was reduced, while thrombospondin 3a (thbs3a) was increased...
July 2017: Open Biology
https://www.readbyqxmd.com/read/28700332/overexpression-of-stathmin-plays-a-pivotal-role-in-the-metastasis-of-esophageal-squamous-cell-carcinoma
#10
Gaijing Han, Zongyong Wu, Nan Zhao, Lanping Zhou, Fang Liu, Fangfei Niu, Yang Xu, Xiaohang Zhao
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a serious malignant tumor that affects human health. We analyzed the correlation between serum stathmin level and ESCC and elucidated the molecular mechanisms of stathmin's promotion of ESCC cell invasion and metastasis. METHODS: Stathmin level in ESCC and healthy control serum were detected by enzyme-linked immunosorbent assay (ELISA), and the clinical parameters were analyzed. We established ESCC cells with stathmin overexpression or knockdown and then evaluated the effects of stathmin on invasion and metastasis in ESCC...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699906/genome-wide-functional-analysis-on-the-molecular-mechanism-of-specifically-biosynthesized-fluorescence-eu-complex
#11
Jing Ye, Xiawei Dong, Xuerui Jiang, Hui Jiang, Chen-Zhong Li, Xuemei Wang
Fluorescence imaging as an attractive diagnostic technique is widely employed for early diagnosis of cancer. Self-biosynthesized fluorescent Eu complex in situ in Hela cells have realized specifically and accurately fluorescence imaging for cancer cells. But the molecular mechanism of the in situ biosynthesized process is still unclear. In order to reveal this mechanism, we have investigated whole-genome expression profiles with cDNA microarray, incubated with Eu solution in Hela cells for 24 h. Methylthiazoltetrazolium (MTT) assay and laser confocal fluorescence microscopy study showed the low cytotoxicity and specifically fluorescence imaging of Eu complex in Hela cells...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699640/lfa-1-activates-focal-adhesion-kinases-fak1-pyk2-to-generate-lat-grb2-skap1-complexes-that-terminate-t-cell-conjugate-formation
#12
Monika Raab, Yuning Lu, Karsten Kohler, Xin Smith, Klaus Strebhardt, Christopher E Rudd
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28697804/ang-ii-at2r-increases-mesenchymal-stem-cell-migration-by-signaling-through-the-fak-and-rhoa-cdc42-pathways-in-vitro
#13
Xiu-Ping Xu, Hong-Li He, Shu-Ling Hu, Ji-Bin Han, Li-Li Huang, Jing-Yuan Xu, Jian-Feng Xie, Ai-Ran Liu, Yi Yang, Hai-Bo Qiu
BACKGROUND: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. METHODS: Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319)...
July 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28693139/azithromycin-effectively-inhibits-tumor-angiogenesis-by-suppressing-vascular-endothelial-growth-factor-receptor-2-mediated-signaling-pathways-in-lung-cancer
#14
Fajiu Li, Jie Huang, Dongyuan Ji, Qinghua Meng, Chuanhai Wang, Shi Chen, Xiaojiang Wang, Zhiyang Zhu, Cheng Jiang, Yi Shi, Shuang Liu, Chenghong Li
Tumor angiogenesis is essential during lung cancer development and targeting angiogenesis may possess a potential therapeutic value. The present study demonstrates that azithromycin, a Food and Drug Administration-approved antibiotic drug, is a novel tumor angiogenesis inhibitor. Azithromycin inhibits capillary network formation of human lung tumor associated-endothelial cells (HLT-ECs) in vitro and in vivo. It significantly inhibits HLT-EC adhesion and vascular endothelial growth factor (VEGF)-induced proliferation of HLT-ECs in a dose-dependent manner without affecting migration...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692661/the-extracellular-matrix-and-focal-adhesion-kinase-signaling-regulate-cancer-stem-cell-function-in-pancreatic-ductal-adenocarcinoma
#15
Asma Begum, Theodore Ewachiw, Clinton Jung, Ally Huang, K Jessica Norberg, Luigi Marchionni, Ross McMillan, Vesselin Penchev, N V Rajeshkumar, Anirban Maitra, Laura Wood, Chenguang Wang, Christopher Wolfgang, Ana DeJesus-Acosta, Daniel Laheru, Irina M Shapiro, Mahesh Padval, Jonathan A Pachter, David T Weaver, Zeshaan A Rasheed, William Matsui
Cancer stem cells (CSCs) play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28688145/therapeutic-concentrations-of-digitoxin-inhibit-endothelial-focal-adhesion-kinase-and-angiogenesis-induced-by-diverse-growth-factors
#16
Annalisa Trenti, Elisabetta Zulato, Lorenza Pasqualini, Stefano Indraccolo, Chiara Bolego, Lucia Trevisi
BACKGROUND AND PURPOSE: Cardiac glycosides are Na(+) /K(+) -ATPases inhibitors used to treat congestive heart failure and cardiac arrhythmias. Epidemiological studies indicate that patients on digitalis therapy are more protected from cancer. Evidence of a selective cytotoxicity against cancer cells has suggested their potential use as anticancer drugs. The effect on angiogenesis of clinically used cardiac glycosides has not been extensively explored. EXPERIMENTAL APPROACH: We studied the effect of digoxin, digitoxin and ouabain on early events of the angiogenic process in human umbilical vein endothelial cells (HUVEC)...
July 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28678601/adhesion-structures-in-leukemia-cells-and-their-regulation-by-src-family-kinases
#17
Pavla Röselová, Adam Obr, Aleš Holoubek, Dana Grebeňová, Kateřina Kuželová
Interaction of leukemia blasts with the bone marrow extracellular matrix often results in protection of leukemia cells from chemotherapy and in persistence of the residual disease which is on the basis of subsequent relapses. The adhesion signaling pathways have been extensively studied in adherent cells as well as in mature hematopoietic cells, but the adhesion structures and signaling in hematopoietic stem and progenitor cells, either normal or malignant, are much less explored. We analyzed the interaction of leukemia cells with fibronectin (FN) using interference reflection microscopy, immunofluorescence, measurement of adherent cell fraction, real-time microimpedance measurement and live cell imaging...
July 5, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28659417/human-adipose-stem-cells-induced-to-osteogenic-differentiation-by-an-innovative-collagen-hydroxylapatite-hybrid-scaffold
#18
Elisa Mazzoni, Antonio D'Agostino, Marco Manfrini, Stefania Maniero, Andrea Puozzo, Elena Bassi, Stefano Marsico, Cinzia Fortini, Lorenzo Trevisiol, Simone Patergnani, Mauro Tognon
Novel biomaterials are of paramount importance for bone regrowth. In this study, we investigated human adipose stem cells (hASCs) for osteogenic, osteoconductivity, and osteoinductivity effects of an innovative collagen/hydroxylapatite hybrid scaffold. In hASCs that were grown on this scaffold, osteogenic genes were analyzed for their expression profiles, together with adhesion and extracellular matrix genes. In hASC integrins, basement membrane constituents and collagens were up-regulated, together with cell proliferation...
June 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28654915/inhibition-of-fak-kinase-activity-preferentially-targets-cancer-stem-cells
#19
Vihren N Kolev, Winnie F Tam, Quentin G Wright, Sean P McDermott, Christian M Vidal, Irina M Shapiro, Qunli Xu, Max S Wicha, Jonathan A Pachter, David T Weaver
Because cancer stem cells (CSCs) have been implicated in chemo-resistance, metastasis and tumor recurrence, therapeutic targeting of CSCs holds promise to address these clinical challenges to cancer treatment. VS-4718 and VS-6063 are potent inhibitors of focal adhesion kinase (FAK), a non-receptor tyrosine kinase that mediates cell signals transmitted by integrins and growth factor receptors. We report here that inhibition of FAK kinase activity by VS-4718 or VS-6063 preferentially targets CSCs, as demonstrated by a panel of orthogonal CSC assays in cell line models and surgically resected primary breast tumor specimens cultured ex vivo...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654796/srpx2-an-independent-prognostic-marker-promotes-cell-migration-and-invasion-in-hepatocellular-carcinoma
#20
Xiaobo Lin, Weiping Chang, Yuan Wang, Ming Tian, Zhaoxiang Yu
Sushi repeat-containing protein X-linked 2 (SRPX2), a novel chondroitin sulfate proteoglycan, is overexpressed in human cancer. Recent studies have reported that SRPX2 overexpression is observed in gastrointestinal cancer, and promotes migration and invasion of cancer cells. While, the clinical significance and biological function of SRPX2 remain rarely known in hepatocellular carcinoma (HCC). Here, we found that the levels of SRPX2 in HCC tissues were notably overexpressed compared to non-cancerous specimens...
June 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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