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Focal adhesion kinase

Emil Rindom, Kristian Vissing
Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS), may contribute to an understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion...
2016: Frontiers in Physiology
Ioanna Antoniades, Panayiota Stylianou, Neophytos Christodoulou, Paris A Skourides
We have previously identified FAK as an important regulator of ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins associate with the basal bodies and their striated rootlets and form complexes named ciliary adhesions (CAs). CAs display similarities with FAs but are established in an integrin independent fashion and are responsible for anchoring basal bodies to the actin cytoskeleton during ciliogenesis, as well as in mature multiciliated cells. FAK downregulation leads to aberrant ciliogenesis due to impaired association between the basal bodies and the actin cytoskeleton, suggesting that FAK is an important regulator of the CA complex...
November 28, 2016: Journal of Biological Chemistry
Shandiz Tehrani, Lauren Davis, William O Cepurna, Tiffany E Choe, Diana C Lozano, Ashley Monfared, Lauren Cooper, Joshua Cheng, Elaine C Johnson, John C Morrison
Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir...
2016: PloS One
Dhaarmini Rajshankar, Yongqiang Wang, Christopher A McCulloch
Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6 kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked, shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced bone volume (4-fold in tails; P < 0...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Dianna M Milewicz, Kathleen M Trybus, Dongchuan Guo, H Lee Sweeney, Ellen Regalado, Kristine Kamm, James T Stull
The importance of maintaining contractile function in aortic smooth muscle cells (SMCs) is evident by the fact that heterozygous mutations in the major structural proteins or kinases controlling contraction lead to the formation of aneurysms of the ascending thoracic aorta that predispose to life-threatening aortic dissections. Force generation by SMC requires ATP-dependent cyclic interactions between filaments composed of SMC-specific isoforms of α-actin (encoded by ACTA2) and myosin heavy chain (MYH11). ACTA2 and MYH11 mutations shown to disrupt this cyclic interaction predispose to thoracic aortic disease...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Chen Zhang, Lüwen Zhou, Fan Zhang, Dongyuan Lü, Ning Li, Lu Zheng, Yanhong Xu, Zhan Li, Shujin Sun, Mian Long
Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edge-on-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Koh Suginami, Yukiyasu Sato, Akihito Horie, Hisanori Matsumoto, Satoru Kyo, Yoshihiko Araki, Ikuo Konishi, Hiroshi Fujiwara
PROBLEM: The human endometrium periodically breaks down and regenerates. As platelets have been reported to contribute to the tissue remodeling process, we examined the possible involvement of platelets in endometrial regeneration. METHOD OF STUDY: The distribution of extravasating platelets throughout the menstrual cycle was immunohistochemically examined using human endometrial tissues. EM-E6/E7/hTERT cells, a human endometrial epithelial cell-derived immortalized cell line, were co-cultured with platelets, and the effects of platelets on the epithelialization response of EM-E6/E7/hTERT cells were investigated by attachment and permeability assays, immunohistochemical staining, and Western blot analysis...
November 21, 2016: American Journal of Reproductive Immunology: AJRI
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: Experimental Hematology
Takasuke Harada, Koichi Yoshimura, Osamu Yamashita, Koshiro Ueda, Noriyasu Morikage, Yasuhiro Sawada, Kimikazu Hamano
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear. APPROACH AND RESULTS: We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages...
November 17, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Haibin Tong, Guiquan Jiang, Dake Qi, Jingfeng Bi, Dan Tian, Xingang Guan, Sheng Zheng, Xin Sun
Adhesive interaction contributes toward tumor metastasis and the transmembrane glycoprotein receptor, integrin has been recognized to mediate the adhesion to extracellular matrix thus upregulating tumor metastasis. In the current study, we evaluated the anti-adhesive mechanisms of a water-soluble polysaccharide (BCP) extracted from Bupleurum chinense. BCP inhibited integrin-mediated adhesion of human melanoma A375 cells to fibronectin but had no effects on nonspecific adhesion to poly-l-lysine. BCP also reduced β1 integrin ligand affinity for GST-FNIII9-10 proteins...
January 20, 2017: Carbohydrate Polymers
Sophie Béraud-Dufour, Chistelle Devader, Fabienne Massa, Morgane Roulot, Thierry Coppola, Jean Mazella
The aim of the present review is to unravel the mechanisms of action of the soluble form of the neurotensin (NT) receptor-3 (NTSR3), also called Sortilin, in numerous physiopathological processes including cancer development, cardiovascular diseases and depression. Sortilin/NTSR3 is a transmembrane protein thought to exert multiple functions both intracellularly and at the level of the plasma membrane. The Sortilin/NTSR3 extracellular domain is released by shedding from all the cells expressing the protein...
November 8, 2016: International Journal of Molecular Sciences
An-Cheng Huang, Mei-Due Yang, Yung-Ting Hsiao, Tzu-Shun Lin, Yi-Shih Ma, Shu-Fen Peng, Te-Chun Hsia, Yih-Dih Cheng, Chao-Lin Kuo, Jing-Gung Chung
ETHNOPHARMACOLOGICAL RELEVANCE: Bufalin, a component of Chan Su (frog), has been shown to have biological activities including anti-tumor effects. Gefitinib has been used as an anti-cancer drug in lung cancer patients; however, some patients eventually become gefitinib resistant. AIM OF THE STUDY: In this study, we investigated anti-metastasis effects of bufalin in gefitinib resistant NCI-H460 lung cancer cells. MATERIALS AND METHODS: The effects of the bufalin in gefitinib resistant NCI-H460 lung cancer cells were investigated on cell viability using flow cytometry...
November 7, 2016: Journal of Ethnopharmacology
Yi-Ting Wang, Hou-Hsien Chiang, Ying-Shing Huang, Chia-Lang Hsu, Po-Jen Yang, Hsueh-Fen Juan, Wei-Shiung Yang
Ribonuclease L (RNase-L) is an endoribonuclease well known for its roles in innate immunity. Recently it has been shown to regulate several cellular functions by modulating the levels of specific mRNAs. In this study, we investigated whether RNase-L may regulate adipocyte functions. We showed that knockdown of RNase-L reduced 3T3-L1 adipocyte differentiation and lipid accumulation. After mRNA profiling, we found that upregulation of Pref-1 mRNA, an inhibitory regulator of adipogenesis, could explain the reduced adipocyte differentiation with RNase-L downregulation...
November 10, 2016: Cell Death & Disease
Dandan Ma, Xiaoxing Kou, Jing Jin, Taotao Xu, Mengjie Wu, Liquan Deng, Lusi Fu, Yi Liu, Gang Wu, Haiping Lu
Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal-regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading...
November 7, 2016: International Journal of Molecular Sciences
Arti V Shinde, Claudio Humeres, Nikolaos G Frangogiannis
Cardiac myofibroblasts play an important role in myocardial remodeling. Although α-smooth muscle actin (α-SMA) expression is the hallmark of mature myofibroblasts, its role in regulating fibroblast function remains poorly understood. We explore the effects of the matrix environment in modulating cardiac fibroblast phenotype, and we investigate the role of α-SMA in fibroblast function using loss- and gain-of-function approaches. In murine myocardial infarction, infiltration of the infarct border zone with abundant α-SMA-positive myofibroblasts was associated with scar contraction...
November 4, 2016: Biochimica et Biophysica Acta
Miodrag Dragoj, Zorica Milosevic, Jasna Bankovic, Nikola Tanic, Milica Pesic, Tijana Stankovic
BACKGROUND: Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells...
November 7, 2016: Cellular Oncology (Dordrecht)
Chunlei Yu, Xiaojie Sun, Yingcai Niu
Curcuma phaeocaulis Val. is a Chinese medicinal herb that is contraindicated during pregnancy for over a thousand years in China. The aims of the present study were to evaluate the effect of curcumol (one of the major components of C. phaeocaulis Val.) on neurite outgrowth and characterize the signal transduction pathways in PC12 cells. Curcumol significantly inhibited neurite outgrowth and cell proliferation, but did not cause cell death at a concentration of 450 μM in differentiated PC12 cells. In addition, curcumol evoked oxidative stress and it was indicated by an elevation in reactive oxygen species (ROS) and lipid peroxidation (LPO)...
November 6, 2016: Toxicology Mechanisms and Methods
Javier A García-Vilas, Almudena Pino-Ángeles, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics simulation approach allows getting further insight on the inhibitory effect of damnacanthal on three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal is a very potent inhibitor of angiogenesis...
November 2, 2016: Cancer Letters
Helmut Bühler, Clemens Hoberg, Khashayar Fakhrian, Irenäus A Adamietz
BACKGROUND/AIM: Various effects on tumor cells have been described for zoledronic acid (ZOL). However, only limited data exist regarding its influence on the motility of tumor cells. Since migration of tumor stem cells is a decisive step in metastasis, we examined whether ZOL reduces their motility. MATERIALS AND METHODS: We investigated the effects of ZOL on stem-like progenitor cells obtained via the formation of spheroids from the human breast cancer cell line MDA-MB 231...
November 2016: In Vivo
Krishna C Vallabhaneni, Meeves-Yoni Hassler, Anu Abraham, Jason Whitt, Yin-Yuan Mo, Azeddine Atfi, Radhika Pochampally
Studies have shown that mesenchymal stem/stromal cells (MSCs) from bone marrow are involved in the growth and metastasis of solid tumors but the mechanism remains unclear in osteosarcoma (OS). Previous studies have raised the possibility that OS cells may receive support from associated MSCs in the nutrient deprived core of the tumors through the release of supportive macromolecules and growth factors either in vesicular or non-vesicular forms. In the present study, we used stressed mesenchymal stem cells (SD-MSCs), control MSCs and OS cells to examine the hypothesis that tumor-associated MSCs in nutrient deprived core provide pro-proliferative, anti-apoptotic, and metastatic support to nearby tumor cells...
2016: PloS One
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