keyword
MENU ▼
Read by QxMD icon Read
search

Focal adhesion kinase

keyword
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#1
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28639351/titanium-released-from-dental-implant-enhances-pre-osteoblast-adhesion-by-ros-modulating-crucial-intracellular-pathways
#2
M C Rossi, Fjb Bezerra, R A Silva, B P Crulhas, Cjc Fernandes, A S Nascimento, V A Pedrosa, P Padilha, W F Zambuzzi
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p<0...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28626446/gnrh-induces-erk-dependent-bleb-formation-in-gonadotrope-cells-involving-recruitment-of-members-of-a-gnrh-receptor-associated-signalosome-to-the-blebs
#3
Liat Rahamim-Ben Navi, Anna Tsukerman, Alona Feldman, Philippa Melamed, Melanija Tomić, Stanko S Stojilkovic, Ulrich Boehm, Rony Seger, Zvi Naor
We have previously described a signaling complex (signalosome) associated with the GnRH receptor (GnRHR). We now report that GnRH induces bleb formation in the gonadotrope-derived LβT2 cells. The blebs appear within ~2 min at a turnover rate of ~2-3 blebs/min and last for at least 90 min. Formation of the blebs requires active ERK1/2 and RhoA-ROCK but not active c-Src. Although the following ligands stimulate ERK1/2 in LβT2 cells: EGF > GnRH > PMA > cyclic adenosine monophosphate (cAMP), they produced little or no effect on bleb formation as compared to the robust effect of GnRH (GnRH > PMA > cAMP > EGF), indicating that ERK1/2 is required but not sufficient for bleb formation possibly due to compartmentalization...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28625871/mir-27-regulates-chondrogenesis-by-suppressing-focal-adhesion-kinase-during-pharyngeal-arch-development
#4
Nergis Kara, Chunyao Wei, Alexander C Commanday, James G Patton
Cranial neural crest cells are a multipotent cell population that generate all the elements of the pharyngeal cartilage with differentiation into chondrocytes tightly regulated by temporal intracellular and extracellular cues. Here, we demonstrate a novel role for miR-27, a highly enriched microRNA in the pharyngeal arches, as a positive regulator of chondrogenesis. Knock down of miR-27 led to nearly complete loss of pharyngeal cartilage by attenuating proliferation and blocking differentiation of pre-chondrogenic cells...
June 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#5
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28621239/a-microrna-signature-associated-with-pathological-complete-response-to-novel-neoadjuvant-therapy-regimen-in-triple-negative-breast-cancer
#6
Raúl García-Vazquez, Erika Ruiz-García, Abelardo Meneses García, Horacio Astudillo-de la Vega, Fernando Lara-Medina, Alberto Alvarado-Miranda, Héctor Maldonado-Martínez, Juan A González-Barrios, Alma D Campos-Parra, Sergio Rodríguez Cuevas, Laurence A Marchat, César López-Camarillo
Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%-85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28619708/arhgap18-downregulation-by-mir-200b-suppresses-metastasis-of-triple-negative-breast-cancer-by-enhancing-activation-of-rhoa
#7
Brock Humphries, Zhishan Wang, Yunfei Li, Jing-Ru Jhan, Yiguo Jiang, Chengfeng Yang
Rho GTPases activated in cancer cells drive proliferation, migration and metastasis. Thus, RhoGAP proteins which negatively regulate Rho GTPases are generally thought to function as tumor suppressors. Here this expectation was challenged by characterization of ARHGAP18, a RhoGAP family member that is selectively overexpressed in highly migratory triple negative breast cancer (TNBC) cells. In human breast tumors, higher ARHGAP18 levels associated with worse overall survival, recurrence-free survival and metastasis-free survival...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28618167/neuropilin-1-regulated-by-mir-320-contributes-to-the-growth-and-metastasis-of-cholangiocarcinoma-cells
#8
Huaqiang Zhu, Xian Jiang, Xu Zhou, Xuesong Dong, Kai Xie, Chuncheng Yang, Hongchi Jiang, Xueying Sun, Jun Lu
BACKGROUND: Neuropilin-1 (NRP-1) activates signaling pathways as multifunctional co-receptors in cancer cells. However, its role and how it is regulated by miRNAs in cholangiocarcinoma (CCA) have not yet been investigated. METHODS: The expression of NRP-1, miR-320 and key molecules involved in cell proliferation, migration and related signaling pathways were detected by immunohistochemistry, immunoblotting and qRT-PCR. Stable transfectants depleted of NRP-1 were generated...
June 15, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28615322/in-vivo-manipulation-of-the-extracellular-matrix-induces-vascular-regression-in-a-basal-chordate
#9
Delany Rodriguez, Brian P Braden, Scott W Boyer, Daryl A Taketa, Leah Setar, Chris Calhoun, Alessandro Di Maio, Adam Langenbacher, Megan T Valentine, Anthony W De Tomaso
We investigated the physical role of the extracellular matrix in vascular homeostasis in the basal chordate Botryllus schlosseri, which has a large, transparent extracorporeal vascular network encompassing areas >100 cm(2) We found that the collagen crosslinking enzyme lysyl oxidase is expressed in all vascular cells, and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 hours. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose-dependent...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28611383/integrin-%C3%AE-2%C3%AE-1-in-nonactivated-conformation-can-induce-focal-adhesion-kinase-signaling
#10
Maria Salmela, Johanna Jokinen, Silja Tiitta, Pekka Rappu, R Holland Cheng, Jyrki Heino
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609185/discovery-and-preclinical-development-of-netarsudil-a-novel-ocular-hypotensive-agent-for-the-treatment-of-glaucoma
#11
Cheng-Wen Lin, Bryan Sherman, Lori A Moore, Carmen L Laethem, Da-Wen Lu, Padmanabhan P Pattabiraman, Ponugoti Vasantha Rao, Mitchell A deLong, Casey C Kopczynski
PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit...
June 13, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28606962/endothelin-1-promotes-vascular-smooth-muscle-cell-migration-across-the-artery-wall-a-mechanism-contributing-to-vascular-remodelling-and-intimal-hyperplasia-in-giant-cell-arteritis
#12
Ester Planas-Rigol, Nekane Terrades-Garcia, Marc Corbera-Bellalta, Ester Lozano, Marco A Alba, Marta Segarra, Georgina Espígol-Frigolé, Sergio Prieto-González, José Hernández-Rodríguez, Sara Preciado, Rodolfo Lavilla, Maria C Cid
BACKGROUND: Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. OBJECTIVE: To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA...
June 12, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28605029/the-pancreatic-cancer-microenvironment-a-true-double-agent
#13
REVIEW
Laleh G Melstrom, Marcela D Salazar, Don J Diamond
The tumor microenvironment in pancreatic cancer is a complex balance of pro- and anti-tumor components. The dense desmoplasia consists of immune cells, extracellular matrix, growth factors, cytokines, and cancer associated fibroblasts (CAF) or pancreatic stellate cells (PSC). There are a multitude of targets including hyaluronan, angiogenesis, focal adhesion kinase (FAK), connective tissue growth factor (CTGF), CD40, chemokine (C-X-C motif) receptor 4 (CXCR-4), immunotherapy, and Vitamin D. The developing clinical therapeutics will be reviewed...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28604765/mlk3-regulates-fra-1-and-mmps-to-drive-invasion-and-transendothelial-migration-in-triple-negative-breast-cancer-cells
#14
C Rattanasinchai, B J Llewellyn, S E Conrad, K A Gallo
Mixed-lineage kinase 3 (MLK3), a mitogen-activated protein kinase kinase kinase (MAP3K), has critical roles in metastasis of triple-negative breast cancer (TNBC), in part by regulating paxillin phosphorylation and focal adhesion turnover. However the mechanisms and the distinct step(s) of the metastatic processes through which MLK3 exerts its influence are not fully understood. Here we report that in non-metastatic, estrogen receptor-positive breast cancer (ER+ BC) cells, induced MLK3 expression robustly upregulates the oncogenic transcription factor, FOS-related antigen-1 (FRA-1), which is accompanied by elevation of matrix metalloproteinases (MMPs), MMP-1 and MMP-9...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28602912/synthetic-8-hydroxydeoxyguanosine-inhibited-metastasis-of-pancreatic-cancer-through-concerted-inhibitions-of-erm-and-rho-gtpase
#15
Jong-Min Park, Young-Min Han, Migyeong Jeong, Myung Hee Chung, Chang Il Kwon, Kwang Hyun Ko, Ki Baik Hahm
8-hydroxydeoxyguanosine (8-OHdG) is generated consequent to oxidative stress, but its paradoxical anti-oxidative, anti-inflammatory, and anti-mutagenic effects via Rho-GTPase inhibition were noted in various models of inflammation and cancer. Metastasis occurs through cell detachment, epithelial-mesenchymal transition (EMT), and cell migration; during these processes, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. In this study, we explored the anti-metastatic mechanisms of 8-OHdG in Panc-1 pancreatic cancer cells...
June 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28600496/dysregulation-of-nuclear-receptor-coup-tfii-impairs-skeletal-muscle-development
#16
Hui-Ju Lee, Chung-Yang Kao, Shih-Chieh Lin, Mafei Xu, Xin Xie, Sophia Y Tsai, Ming-Jer Tsai
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been shown to inhibit myogenesis and skeletal muscle metabolism in vitro. However, its precise role and in vivo function in muscle development has yet to be clearly defined. COUP-TFII protein expression level is high in undifferentiated progenitors and gradually declines during differentiation, raising an important question of whether downregulation of COUP-TFII expression is required for proper muscle cell differentiation. In this study, we generated a mouse model ectopically expressing COUP-TFII in myogenic precursors to maintain COUP-TFII activity during myogenesis and found that elevated COUP-TFII activity resulted in inefficient skeletal muscle development...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596238/loss-of-%C3%AE-pix-inhibits-focal-adhesion-disassembly-and-promotes-keratinocyte-motility-via-myosin-light-chain-activation
#17
Sho Hiroyasu, Gregory P Stimac, Susan B Hopkinson, Jonathan C R Jones
During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor β-PIX. In fibroblasts, β-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, β-PIX localizes to FAs. To study β-PIX functions, we generated β-PIX knockdown keratinocytes. During wound closure of β-PIX knockdown cell monolayers, disassembly of FA is impaired and their number and size are increased...
June 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28592633/the-phospho-caveolin-1-scaffolding-domain-dampens-force-fluctuations-in-focal-adhesions-and-promotes-cancer-cell-migration
#18
Fanrui Meng, Sandeep Saxena, Youtao Liu, Bharat Joshi, Timothy H Wong, Jay Shankar, Leonard J Foster, Pascal Bernatchez, Ivan R Nabi
Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly-conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82-101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD competing peptides, that Src kinase-dependent pY14Cav1 regulation of focal adhesion protein stabilization, focal adhesion tension and cancer cell migration is CSD-dependent. Quantitative proteomic analysis of Cav1-GST (1-101 amino acids) pulldowns showed 6-fold increased binding of vinculin and, to a lesser extent, α-actinin, talin and filamin, to phosphomimetic Cav1Y14D relative to non-phosphorylatable Cav1Y14F...
June 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28591722/critical-role-of-%C3%AE-1-integrin-in-postnatal-beta-cell-function-and-expansion
#19
Jason Peart, Jinming Li, Hojun Lee, Matthew Riopel, Zhi-Chao Feng, Rennian Wang
β1 integrin is essential for pancreatic beta-cell development and maintenance in rodents and humans. However, the effects of a temporal beta-cell specific β1 integrin knockout on adult islet function are unknown. We utilized a mouse insulin 1 promoter driven tamoxifen-inducible Cre-recombinase β1 integrin knockout mouse model (MIPβ1KO) to investigate β1 integrin function in adult pancreatic beta-cells. Adult male MIPβ1KO mice were significantly glucose intolerant due to impaired glucose-stimulated insulin secretion in vivo and ex vivo at 8 weeks post-tamoxifen...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591616/focal-adhesion-kinase-the-reversible-molecular-mechanosensor
#20
Samuel Bell, Eugene M Terentjev
Sensors are the first element of the pathways that control the response of cells to their environment. Protein complexes that produce or enable a chemical signal in response to a mechanical stimulus are called "mechanosensors". In this work, we develop a theoretical model describing the physical mechanism of a reversible single-molecule stiffness sensor. Although this has the potential for general application, here we apply the model to focal adhesion kinase, which initiates the chemical signal in its active phosphorylated conformation, but can spontaneously return to its closed folded conformation...
June 6, 2017: Biophysical Journal
keyword
keyword
50900
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"