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Niya Xiong, Shun Li, Kai Tang, Hongxia Bai, Yueting Peng, Hong Yang, Chunhui Wu, Yiyao Liu
Tumor cells translocating to distant sites are subjected to hemodynamic shear forces during their passage in the blood vessels. Low shear stress (LSS) plays a critical role in the regulation of various aspects of tumor cells functions, including motility and adhesion. Beyond its structural role, caveolin-1 (Cav-1), the important component of caveolae, represents a modulator of several cancer-associated functions as tumor progression and metastasis. However, the role of Cav-1 in regulating tumor cells response to shear stress remains poorly explored...
October 20, 2016: Biochimica et Biophysica Acta
Hongyu Sun, Jiajia Tang, Yongchao Mou, Jing Zhou, Linlin Qu, Kayla Duval, Zhu Huang, Ning Lin, Ruiwu Dai, Chengxiao Liang, Zi Chen, Lijun Tang, Fuzhou Tian
: Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs...
October 18, 2016: Acta Biomaterialia
Jianhua Zhu, Jing Luo, Yongchao Li, Min Jia, Yueqin Wang, Yan Huang, Shuhong Ke
High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein with multi-functions and plays an important role in tumorigenesis and metastasis in various human cancers. In the present study, we found that HMGB1 induced migration of in human non-small cell lung cancer (NSCLC) cells by up-regulating integrin αvβ3 expression. Further investigation evidenced that HMGB1 activated Toll-like receptor 4 (TLR4) and NF-κB, which was responsible for αvβ3 up-regulation. Furthermore, HMGB1-induced integrin αvβ3 expression led to focal adhesion kinase (FAK) phosphorylation and increased paxillin and talin mRNA expression...
October 18, 2016: Biochemical and Biophysical Research Communications
Yuanyuan Ji, Zhidong Wang, Zongfang Li, Na Huang, Haiyan Chen, Baohua Li, Bo Hui
Emerging evidence confirms that insulin-like growth factor -II (IGF-II), oncogenes C-myc and N-ras are an essential regulator for development and growth in hepatocellular carcinoma (HCC). Although our previous study also indicated that IGF-II might upregulate levels of oncogenes C-myc and N-ras in hepatoma carcinoma cells, the molecular mechanism had not been fully elucidated. Herein, we successfully silenced IGF-II expression in SMCC-7721 cells by small RNA interference. Functional analysis showed that knockdown of IGF-II significantly suppressed growth and proliferation of SMMC-7721 cells and decreased C-myc and N-ras mRNA and protein levels...
October 18, 2016: Cytokine
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Qi Cao, Zheng-Dao Mao, Yu-Jia Shi, Yi Chen, Yun Sun, Qian Zhang, Lei Song, Li-Ping Peng
OBJECTIVE: To investigate the effects of microRNA-7 (miR-7) on the proliferation, migration and invasion of non-small cell lung cancer NSCLC) cells by targeting FAK through ERK/MAPK signaling pathway. METHODS: NSCLC tissues and adjacent normal tissues were obtained from 160 NSCLC patients after operation. NSCLC cell lines (A549, H1299 and H1355) and a normal human fetal lung fibroblast cell line (MRC-5) were obtained. NSCLC cells were assigned into miR-7 inhibitors, miR-7 mimics, blank, miR-7 mimics control, miR-7 inhibitors control, FAK siRNA and miR-7 inhibitors + FAK siRNA groups...
October 15, 2016: Oncotarget
Binod Kumar, Dipanjan Dutta, Jawed Iqbal, Mairaj Ahmed Ansari, Arunava Roy, Leela Chikoti, Gina Pisano, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells...
October 2016: PLoS Pathogens
Erik Richter, Manuela Harms, Katharina Ventz, Rolf Nölker, Martin J Fraunholz, Jörg Mostertz, Falko Hochgräfe
Internalization of Staphylococcus aureus by non-professional phagocytic cells is a major suspected cause of persistent and difficult-to-treat infections, including pneumonia. In this study, we established an infection model with 16HBE14o- human bronchial epithelial cells and demonstrated internalization, escape from phagosomal clearance and intracellular replication of S. aureus HG001 within the first four hours post-infection. We used quantitative phosphoproteomics to identify characteristic signaling networks in the host at different infection stages...
October 20, 2016: Journal of Proteome Research
Marc A Antonyak, Richard A Cerione
Intercellular communication mediated by extracellular vesicles (EVs), membrane-enclosed packages released by cells, plays important roles in several physiological and pathological settings. Moreover, EVs have been shown to contain molecular signatures that reflect their cell of origin, raising the possibility that EV cargo could potentially be used to diagnose disease. However, for this to occur, a better understanding of the differences between EVs generated by normal and diseased cells is needed. We recently discovered that the content and function of one major class of EVs, microvesicles (MVs), changes upon the induction of oncogenic transformation...
October 18, 2016: Small GTPases
Jasjeet Bhullar, Veena M Bhopale, Ming Yang, Kinjal Sethuraman, Stephen R Thom
This investigation explored the mechanism for microparticles (MPs) production by human and murine platelets exposed to high pressures of inert gases. Results demonstrate that MPs production occurs via an oxidative stress response in a dose-dependent manner and follows the potency series N2 > Ar > He. Gases with higher van der Waals volumes or polarizability such as SF6 and N2O, or hydrostatic pressure, do not cause MPs production. Singlet O2 is generated by N2, Ar and He, which is linked to NADPH oxidase (NOX) activity...
October 14, 2016: Free Radical Biology & Medicine
Fa-Min Zeng, Yang-Min Xie, Lian-Di Liao, Li-Yan Li, Bo Chen, Jian-Jun Xie, Li-Yan Xu, En-Min Li
The key molecular events that contribute to tumorigenesis are incompletely understood. The aim of the present study was to characterize and compare the biological phenotypes of three human telomerase reverse transcriptase (hTERT) and/or human papillomavirus 16 E6 and E7‑immortalized esophageal epithelial cell lines, NE2‑hTERT (NE2), NE3‑E6E7‑hTERT (NE3) and NEcA6‑E6E7‑hTERT (NEcA6). The present study used soft‑agar colony formation assays, tumorigenicity assays in nude mice, and cell proliferation, adhesion and migration assays to identify the biological characteristics of NE2, NE3 and NEcA6 cells...
October 6, 2016: Molecular Medicine Reports
Husni Elbahesh, Silke Bergmann, Charles J Russell
Influenza A viruses (IAVs) cause numerous pandemics and yearly epidemics resulting in ~500,000 annual deaths globally. IAV modulates cellular signaling pathways at every step of the infection cycle. Focal adhesion kinase (FAK) has been shown to play a critical role in endosomal trafficking of influenza A viruses, yet it is unclear how FAK kinase activity regulates IAV replication. Using mini-genomes derived from H1N1, H5N1 and H7N9 viruses, we dissected RNA replication by IAVs independent of viral entry or release...
October 13, 2016: Virology
Naotaka Nakazawa, Aneesh R Sathe, G V Shivashankar, Michael P Sheetz
Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
Wen-Bin Ou, Minmin Lu, Grant Eilers, Hailong Li, Jiongyan Ding, Xuli Meng, Yuehong Wu, Quan He, Qing Sheng, Hai-Meng Zhou, Jonathan A Fletcher
BACKGROUND: Improved mesothelioma patient survival will require development of novel and more effective pharmacological interventions. TP53 genomic mutations are uncommon in mesothelioma, and recent data indicate that p53 remains functional, and therefore is a potential therapeutic target in these cancers. In addition, the tumour suppressor NF2 is inactivated by genomic mechanisms in more than 80% of mesothelioma, causing upregulation of FAK activity. Because FAK is a negative regulator of p53, NF2 regulation of FAK-p53-MDM2 signalling loops were evaluated...
October 13, 2016: British Journal of Cancer
Kamil Kowalski, Aleksandra Kołodziejczyk, Maria Helena Sikorska, Jagoda Płaczkiewicz, Paulina Cichosz, Magdalena Kowalewska, Wladyslawa Streminska, Katarzyna Janczyk-Ilach, Marta Koblowska, Anna Fogtman, Roksana Iwanicka-Nowicka, Maria A Ciemerych, Edyta Brzoska
The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor -1) increased migration of stem cells and their fusion with myoblasts in vitro...
October 13, 2016: Cell Adhesion & Migration
J C Soria, H K Gan, S P Blagden, R Plummer, H T Arkenau, M Ranson, T R J Evans, G Zalcman, R Bahleda, A Hollebecque, C Lemech, E Dean, J Brown, D Gibson, V Peddareddigari, S Murray, N Nebot, J Mazumdar, L Swartz, K R Auger, R A Fleming, R Singh, M Millward
BACKGROUND: Focal adhesion kinase (FAK) is important in cancer growth, survival, invasion, and migration. The purpose of this study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the FAK inhibitor, GSK2256098, in cancer patients. PATIENTS AND METHODS: The dose of GSK2256098 was escalated, in cohorts of patients with advanced cancer, from 80 to 1500 mg, oral twice daily (BID), until the MTD was determined...
October 11, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Hui Zhao, Wei Wang, Jie Zhang, Tuo Liang, Guang-Pu Fan, Zhi-Wei Wang, Pei-De Zhang, Xu Wang, Jing Zhang
BACKGROUND: Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis. METHOD: Eight-week-old cTnTR(141W) transgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression...
2016: American Journal of Translational Research
Daria R Bulanova, Yevhen A Akimov, Anne Rokka, Teemu D Laajala, Tero Aittokallio, Petri Kouvonen, Teijo Pellinen, Sergey G Kuznetsov
G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1...
October 7, 2016: Cell Adhesion & Migration
Takayuki Kishi, Taira Mayanagi, Sadahiro Iwabuchi, Toshihide Akasaka, Kenji Sobue
The regulation of cell-substrate adhesion is tightly linked to the malignant phenotype of tumor cells and plays a role in their migration, invasion, and metastasis. Focal adhesions (FAs) are dynamic adhesion structures that anchor the cell to the extracellular matrix. Myocardin-related transcription factors (MRTFs), co-regulators of the serum response factor (SRF), regulate expression of a set of genes encoding actin cytoskeletal/FA-related proteins. Here we demonstrated that the forced expression of a constitutively active MRTF-A (CA-MRTF-A) in B16F10 melanoma cells induced the up-regulation of actin cytoskeletal and FA proteins, resulting in FA reorganization and the suppression of cell migration...
September 30, 2016: Oncotarget
Mengsi Hu, Minghua Fan, Junhui Zhen, Jiangong Lin, Qun Wang, Zhimei Lv, Rong Wang
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that regulates cell adhesion, proliferation and differentiation. In the present study, a rat model of high fat diet-induced hypercholesterolaemia was established to investigate the involvement of FAK in lipid disorder-related kidney diseases. We showed focal fusion of podocyte foot process that occurred at as early as 4 weeks in rats consuming high fat diet, preceding the onset of proteinuria when aberrant phosphorylation of FAK was found...
October 5, 2016: Journal of Cellular and Molecular Medicine
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