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https://www.readbyqxmd.com/read/28331230/dentin-sialoprotein-facilitates-dental-mesenchymal-cell-differentiation-and-dentin-formation
#1
Wentong Li, Lei Chen, Zhuo Chen, Lian Wu, Junsheng Feng, Feng Wang, Lisa Shoff, Xin Li, Kevin J Donly, Mary MacDougall, Shuo Chen
Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its target gene expression. DSP mutations cause dentin genetic diseases. However, mechanisms of DSP in controlling dental mesenchymal cell differentiation are unknown. Using DSP as bait, we screened a protein library from mouse odontoblastic cells and found that DSP is a ligand and binds to cell surface receptor, occludin. Further study identified that the C-terminal DSP domain(aa 363-458) interacts with the occludin extracellular loop 2(aa 194-241)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331074/osteopontin-inhibits-osteoblast-responsiveness-through-the-downregulation-of-focal-adhesion-kinase-mediated-by-the-induction-of-low-molecular-weight-protein-tyrosine-phosphatase
#2
Joji Kusuyama, Kenjiro Bandow, Tomokazu Ohnishi, Mitsuhiro Hisadome, Kaori Shima, Ichiro Semba, Tetsuya Matsuguchi
Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone legions such as rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here, we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 (Nos1) and Nos2 was increased by low intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts...
March 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28322779/semisynthetic-oleanane-triterpenoids-inhibit-migration-and-invasion-of-human-breast-cancer-cells-through-downregulated-expression-of-the-itgb1-ptk2-pxn-pathway
#3
Natalia Lisiak, Anna Paszel-Jaworska, Ewa Toton, Błażej Rubiś, Martyna Pakuła, Barbara Bednarczyk-Cwynar, Lucjusz Zaprutko, Maria Rybczyńska
This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells...
March 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28315854/mutation-of-n-linked-glycosylation-in-epcam-affected-cell-adhesion-in-breast-cancer-cells
#4
Xue Liu, Jiujiao Gao, Yan Sun, Dandan Zhang, Tingjiao Liu, Qiu Yan, Xuesong Yang
EpCAM expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin...
March 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28314844/abituzumab-targeting-of-alphav-class-integrins-inhibits-prostate-cancer-progression
#5
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin alpha V subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine if abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin alpha V impacts, prostate cancer (PCa) progression. To evaluate this, PCa cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt and ERK were determined...
March 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28314297/expression-and-clinical-significance-of-concomitant-fak-src-and-p-paxillin-in-mobile-tongue-squamous-cell-carcinoma
#6
Stamatios Theocharis, Ioly Kotta-Loizou, Constantinos Giaginis, Paraskevi Alexandrou, Eugene Danas, Gerasimos Tsourouflis, Nikolaos Tsoukalas, Robert H A Coutts, Jason Tasoulas, Jerzy Klijanienko
BACKGROUND/AIM: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: FAK, SRC and phospho-paxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303961/the-metabolic-waste-ammonium-regulates-mtorc2-and-mtorc1-signaling
#7
Ahmad Merhi, Paul Delrée, Anna Maria Marini
Two structurally and functionally distinct mammalian TOR complexes control cell growth and metabolism in physiological and pathological contexts including cancer. Upregulated glutaminolysis is part of the metabolic reprogramming occurring in cancer, providing fuels for growth but also liberating ammonium, a potent neurotoxic waste product. Here, we identify ammonium as a novel dose-dependent signal mediating rapid mTORC2 activation and further regulating mTORC1. We show that ammonium induces rapid RICTOR-dependent phosphorylation of AKT-S473, a process requiring the PI3K pathway and further involving the Src-family kinase YES1, the FAK kinase and the ITGβ1 integrin...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#8
Ben Stutchbury, Paul Atherton, Ricky Tsang, De-Yao Wang, Christoph Ballestrem
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. Using fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP), we found that the mobility of core FA proteins correlates with protein function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting they are involved in sensing the rigidity of the extracellular environment...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28293103/protective-influence-of-hyaluronic-acid-on-focal-adhesion-kinase-activity-in-human-skin-fibroblasts-exposed-to-ethanol
#9
Magdalena Donejko, Edyta Rysiak, Elżbieta Galicka, Robert Terlikowski, Edyta Katarzyna Głażewska, Andrzej Przylipiak
AIM: The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. MATERIALS AND METHODS: Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28290610/kindlin-1-contributes-to-egf-induced-re-epithelialization-in-skin-wound-healing
#10
Congcong Shen, Linlin Sun, Ningwen Zhu, Fazhi Qi
The commercial use of epidermal growth factor (EGF) is extensive and has been shown to be effective for skin wound healing in clinical practice. There is evidence to indicate that the topical administration of EGF significantly accelerates re-epithelialization by promoting keratinocyte mitogenesis and migration following acute injury; however, the mechanisms involved remain to be elucidated. Thus, in this study, we focused on Kindlin-1, a four-point-one, ezrin, radixin, moesin (FERM)-domain-containing adaptor protein, and report its contribution to EGF-induced re-epithelialization in skin wound healing...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289710/targeting-adhesion-signaling-in-kras-lkb1-mutant-lung-adenocarcinoma
#11
Melissa Gilbert-Ross, Jessica Konen, Junghui Koo, John Shupe, Brian S Robinson, Walter Guy Wiles, Chunzi Huang, W David Martin, Madhusmita Behera, Geoffrey H Smith, Charles E Hill, Michael R Rossi, Gabriel L Sica, Manali Rupji, Zhengjia Chen, Jeanne Kowalski, Andrea L Kasinski, Suresh S Ramalingam, Haian Fu, Fadlo R Khuri, Wei Zhou, Adam I Marcus
Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28287129/akt1-and-akt2-isoforms-play-distinct-roles-during-breast-cancer-progression-through-the-regulation-of-specific-downstream-proteins
#12
Marina Riggio, María C Perrone, María L Polo, María J Rodriguez, María May, Martín Abba, Claudia Lanari, Virginia Novaro
The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286026/clonorchis-sinensis-excretory-secretory-products-promote-the-migration-and-invasion-of-cholangiocarcinoma-cells-by-activating-the-integrin-%C3%AE-4-fak-src-signaling-pathway
#13
Jhang Ho Pak, Qudsia Bashir, In Ki Kim, Sung-Jong Hong, Sejung Maeng, Young Yil Bahk, Tong-Soo Kim
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion...
March 7, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28285878/stem-cell-factors-based-identification-and-functional-properties-of-in%C3%A2-vitro-selected-subpopulations-of-malignant-mesothelioma-cells
#14
Walter Blum, László Pecze, Emanuela Felley-Bosco, Licun Wu, Marc de Perrot, Beat Schwaller
Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models...
March 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28284838/prl-3-ptp4a3-phosphatase-regulates-integrin-%C3%AE-1-in-adhesion-structures-during-migration-of-human-ocular-melanoma-cells
#15
Malika Foy, Océane Anézo, Simon Saule, Nathalie Planque
In a previous transcriptomic analysis of 63 ocular melanomas of the uvea, we found that expression of the PRL-3/PTP4A3 gene, encoding a phosphatase that is anchored to the plasma membrane, was associated with the risk of metastasis, and a poor prognosis. We also showed that PRL-3 overexpression in OCM-1 ocular melanoma cells significantly increased cell migration in vitro and invasiveness in vivo, suggesting a direct role for PRL-3 in the metastatic spreading of uveal melanoma. Here, we aimed to identify PRL-3 substrates at the plasma membrane involved in adhesion to the extracellular matrix...
March 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28284808/synthesis-of-novel-1-2-4-triazine-scaffold-as-fak-inhibitors-with-antitumor-activity
#16
Pascal Dao, Daniel Lietha, Mélanie Etheve-Quelquejeu, Christiane Garbay, Huixiong Chen
A series of 1,3,5-triazinic inhibitors of focal adhesion kinase (FAK) has recently been shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. In this report, we designed and synthesized a series of new compounds containing a 1,2,4-triazine core as novel scaffold for FAK inhibitors. These compounds displayed 10(-7)M IC50 values, and the best one showed IC50 value of 0.23μM against FAK enzymatic activity. Among them, several inhibitors potently inhibited the proliferation of glioblastoma (U-87MG) and colon (HCT-116) cancer cell lines...
February 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28283477/lung-epithelial-cell-focal-adhesion-kinase-signaling-inhibits-lung-injury-and-fibrosis
#17
Amanda K Wheaton, Manisha Agarwal, Shijing Jia, Kevin K Kim
Progressive pulmonary fibrosis is a devastating consequence of many acute and chronic insults to the lung. Lung injury leads to alveolar epithelial cell (AEC) death, destruction of the basement membrane and activation of TGFβ. There is subsequent resolution of the injury and a coordinated and concurrent initiation of fibrosis. Both of these processes may involve activation of similar intracellular signaling pathways regulated in part by dynamic changes to the extracellular matrix. Matrix signaling can augment the pro-fibrotic fibroblast response to TGFβ...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28280091/dual-inhibition-of-egfr-and-c-src-by-cetuximab-and-dasatinib-combined-with-folfox-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#18
Christine Parseghian, Nila U Parikh, Ji Yuan Wu, Zhi-Qin Jiang, Laura D Henderson, Feng Tian, Brice Pastor, Marc Ychou, Kanwal Raghav, Arvind Dasari, David Fogelman, Anastasia Katsiampoura, David G Menter, Robert A Wolff, Cathy Eng, Michael J Overman, Alain R Thierry, Gary E Gallick, Scott Kopetz
BACKGROUND: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. METHODS: We performed a phase IB/II study of 77 patients with previously-treated mCRC. Primary objectives were to determine the MTD, dose-limiting-toxicities, pharmacodynamics, and efficacy...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28273099/dynamin2-controls-rap1-activation-and-integrin-clustering-in-human-t-lymphocyte-adhesion
#19
Felix J Eppler, Thomas Quast, Waldemar Kolanus
Leukocyte trafficking is crucial to facilitate efficient immune responses. Here, we report that the large GTPase dynamin2, which is generally considered to have a key role in endocytosis and membrane remodeling, is an essential regulator of integrin-dependent human T lymphocyte adhesion and migration. Chemical inhibition or knockdown of dynamin2 expression significantly reduced integrin-dependent T cell adhesion in vitro. This phenotype was not observed when T cells were treated with various chemical inhibitors which abrogate endocytosis or actin polymerization...
2017: PloS One
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#20
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan Mak, Hong Mu, Vivian Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 x 10-4) and relapse (P = 0...
March 7, 2017: Molecular Cancer Therapeutics
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