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Focal adhesion kinase

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https://www.readbyqxmd.com/read/29138211/transcriptome-sequencing-of-the-naked-mole-rat-heterocephalus-glaber-and-identification-of-hypoxia-tolerance-genes
#1
Bang Xiao, Li Li, Chang Xu, Shanmin Zhao, Lifang Lin, Jishuai Cheng, Wenjing Yang, Wei Cong, Guanghan Kan, Shufang Cui
The naked mole rat (NMR; Heterocephalus glaber) is a small rodent species found in regions of Kenya, Ethiopia and Somalia. It has a high tolerance for hypoxia and is thus, considered one of the most important natural models for studying hypoxia tolerance mechanisms. The various mechanisms underlying the NMR's hypoxia tolerance are beginning to be understood at different levels of organization, and next-generation sequencing methods promise to expand this understanding to the level of gene expression. In this study, we examined the sequence and transcript abundance data of the muscle transcriptome of NMRs exposed to hypoxia using the Illumina HiSeq 2500 system to clarify the possible genomic adaptive responses to the hypoxic underground surroundings...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29137326/overexpression-of-carbonic-anhydrase-ix-induces-cell-motility-by-activating-matrix-metalloproteinase-9-in-human-oral-squamous-cell-carcinoma-cells
#2
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133485/pyk2-and-fak-differentially-regulate-invadopodia-formation-and-function-in-breast-cancer-cells
#3
Alessandro Genna, Stefanie Lapetina, Nikola Lukic, Shams Twafra, Tomer Meirson, Ved P Sharma, John S Condeelis, Hava Gil-Henn
The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but the mechanism by which it potentiates tumor cell invasiveness is unclear at present. Using high-throughput protein array screening and bioinformatic analysis, we identified cortactin as a novel substrate and interactor of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 colocalizes with cortactin to invadopodia of invasive breast cancer cells, where it mediates epidermal growth factor-induced cortactin tyrosine phosphorylation both directly and indirectly via Src-mediated Abl-related gene (Arg) activation, leading to actin polymerization in invadopodia, extracellular matrix degradation, and tumor cell invasion...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29131527/3d-matrix-embedding-inhibits-cycloheximide-mediated-sensitization-to-tnf-alpha-induced-apoptosis-of-human-endothelial-cells
#4
Michael Saemisch, Markus Nickmann, Lisa Riesinger, Elazer R Edelman, Heiko Methe
The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis...
November 13, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29130389/anti-cancer-effects-of-f16-a-novel-vascular-endothelial-growth-factor-receptor-specific-inhibitor
#5
Appu Rathinavelu, Khalid Alhazzani, Sivanesan Dhandayuthapani, Thanigaivelan Kanagasabai
Vascular endothelial growth factor receptor-2 is a dynamic target for therapeutic intervention in various types of cancers. This study was aimed to explore the anti-angiogenic activity of a novel vascular endothelial growth factor receptor-specific inhibitor named F16 in both in vitro and in vivo experimental models. This compound effectively reduced cell proliferation, tube formation, and migration of human umbilical vein endothelial cells in a concentration-dependent manner by directly inhibiting vascular endothelial growth factor binding and subsequent vascular endothelial growth factor receptor-2 phosphorylation...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29127427/amniotic-membrane-promotes-focal-adhesion-remodeling-to-stimulate-cell-migration
#6
Ángel Bernabé-García, Sergio Liarte, Jose M Moraleda, Gregorio Castellanos, Francisco J Nicolás
During wound healing, the migration of keratinocytes onto newly restored extracellular matrix aims to reestablish continuity of the epidermis. The application of amniotic membrane (AM) to chronic, deep traumatic, non-healing wounds has proven successful at stimulating re-epithelialization. When applied on epithelial cell cultures, AM activates extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases 1/2 (JNK1/2), with the overexpression and phosphorylation of c-Jun along the wound edge...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116364/low-density-lipoprotein-receptor-related-protein-1-couples-%C3%AE-1-integrin-activation-to-degradation
#7
Lukasz Wujak, Ralph T Böttcher, Oleg Pak, Helena Frey, Elie El Agha, Ying Chen, Sigrid Schmitt, Saverio Bellusci, Liliana Schaefer, Norbert Weissmann, Reinhard Fässler, Malgorzata Wygrecka
Low density lipoprotein receptor-related protein (LRP) 1 modulates cell adhesion and motility under normal and pathological conditions. Previous studies documented that LRP1 binds several integrin receptors and mediates their trafficking to the cell surface and endocytosis. However, the mechanism by which LRP1 may regulate integrin activation remains unknown. Here we report that LRP1 promotes the activation and subsequent degradation of β1 integrin and thus supports cell adhesion, spreading, migration and integrin signaling on fibronectin...
November 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29115617/three-dimensional-hydrogel-is-suitable-for-targeted-investigation-of-amoeboid-migration-of-glioma-cells
#8
Yubao Huang, Luqing Tong, Li Yi, Chen Zhang, Long Hai, Tao Li, Shengping Yu, Wei Wang, Zhennan Tao, Haiwen Ma, Peidong Liu, Yang Xie, Xuejun Yang
Glioblastoma (GBM) invasion and migration are key biological behaviors leading to refractoriness to current therapies and infiltration into the non‑tumor brain parenchyma. GBM cell migration is strongly dependent on tumor architecture in vivo, which is absent in traditional two‑dimensional (2D) monolayer culture. The present study applied a three‑dimensional (3D) hydrogel model to rebuild the tumor architecture in vitro. Treatment with NSC23766, a specific inhibitor of Ras‑related C3 botulinum toxin substrate 1 (Rac1), inhibited the mesenchymal invasiveness however triggered the amoeboid motility called mesenchymal‑amoeboid transition (MAT)...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115573/fibroblast-activation-protein-%C3%AE-promotes-the-growth-and-migration-of-lung-cancer-cells-via-the-pi3k-and-sonic-hedgehog-pathways
#9
Jun Jia, Tracey A Martin, Lin Ye, Lin Meng, Nan Xia, Wen G Jiang, Xiaodong Zhang
A characteristic of the epithelial-to-mesenchymal transition in cancer cells is the upregulation of mesenchymal markers. Fibroblast activation protein α (FAPα) is predominantly expressed by stromal fibroblasts. Previous studies have demonstrated that FAPα is also expressed by certain epithelium-derived cancer cells and is involved in the regulation of certain signaling pathways. One of our previous studies showed that FAPα promoted the proliferation of breast cancer cells via the phosphatidylinositol-3-kinase (PI3K) signaling pathway...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29115463/ganoderma-lucidum-polysaccharide-inhibits-prostate-cancer-cell-migration-via-the-protein-arginine-methyltransferase-6-signaling-pathway
#10
Xiaohui Zhao, Dayu Zhou, Yunen Liu, Chun Li, Xiaoguang Zhao, Ying Li, Wei Li
Prostate cancer is one of the most common types of malignant tumor of men worldwide and the incidence and mortality rate is gradually increasing. At present, the molecular mechanisms of growth and migration in human prostate cancer have not been completely elucidated. Studies have demonstrated that Ganoderma lucidum polysaccharides (GLP) can inhibit cancer. Therefore the present study investigated the effect and molecular mechanism of GLP on cell growth and migration of LNCaP human prostate cancer cells. LNCaP cells were transfected with either a protein arginine methyltransferase 6 (PRMT6) overexpression plasmid or PRMT6 small interfering (si)RNA...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115292/fibronectin-bound-%C3%AE-5%C3%AE-1-integrins-sense-load-and-signal-to-reinforce-adhesion-in-less-than-a-second
#11
Nico Strohmeyer, Mitasha Bharadwaj, Mercedes Costell, Reinhard Fässler, Daniel J Müller
Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0...
November 6, 2017: Nature Materials
https://www.readbyqxmd.com/read/29114068/receptor-tyrosine-kinase-activation-of-rhoa-is-mediated-by-akt-phosphorylation-of-dlc1
#12
Brajendra K Tripathi, Tiera Grant, Xiaolan Qian, Ming Zhou, Philipp Mertins, Dunrui Wang, Alex G Papageorge, Sergey G Tarasov, Kent W Hunter, Steven A Carr, Douglas R Lowy
We report several receptor tyrosine kinase (RTK) ligands increase RhoA-guanosine triphosphate (GTP) in untransformed and transformed cell lines and determine this phenomenon depends on the RTKs activating the AKT serine/threonine kinase. The increased RhoA-GTP results from AKT phosphorylating three serines (S298, S329, and S567) in the DLC1 tumor suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions. Phosphorylation of the serines, located N-terminal to the DLC1 RhoGAP domain, induces strong binding of that N-terminal region to the RhoGAP domain, converting DLC1 from an open, active dimer to a closed, inactive monomer...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29113282/common-mechanism-of-pathogenesis-in-various-types-of-metastatic-osteosarcoma
#13
Dongqi Wang, Zongrang Song, Zhan Wang
The present study aimed to investigate the common metastatic mechanism in various types of metastatic osteosarcoma (OS). Gene expression profiles generated from the metastatic OS KHOS and KRIB cell lines and the non-metastatic OS HOS cell line were compared. Two groups of differentially expressed genes (DEGs) between KHOS or KRIB and HOS were screened (P<0.01 and |fold change| ≥2) and then underwent Gene Ontology (GO) and pathway enrichment analyses. Subsequently, the protein-protein interaction (PPI) network was constructed and the subnetwork was mined...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113234/upregulation-of-tctp-is-associated-with-cholangiocarcinoma-progression-and-metastasis
#14
Nattaporn Phanthaphol, Anchalee Techasen, Watcharin Loilome, Suyanee Thongchot, Raynoo Thanan, Sakkarn Sungkhamanon, Narong Khuntikeo, Puangrat Yongvanit, Nisana Namwat
In order to investigate the role of translationally-controlled tumor protein (TCTP) in cholangiocarcinoma (CCA) progression and metastasis, TCTP protein staining in paraffin-embedded sections of human CCA tissue samples was examined using immunohistochemistry, and its expression was subsequently compared with clinicopathological parameters. Small interfering RNA (siRNA) targeting TCTP (siTCTP) were transfected into CCA cell lines to evaluate its effects on cellular functions. The proliferation, tumorigenicity and migration abilities of the transfected cells were measured using sulforhodamine B, clonogenic and would healing assays, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113181/microrna-profiling-and-bioinformatics-analyses-reveal-the-potential-roles-of-micrornas-in-chordoma
#15
Kangwu Chen, Hao Chen, Kai Zhang, Siwei Sun, Jianqiang Mo, Jian Lu, Zhonglai Qian, Huilin Yang
Chordoma is a rare aggressive bone tumor arising from remnants of the notochord, and patients with chordoma have a poor prognosis. However, the unique expression profiles of microRNAs (miRNAs/miRs) and their downstream signaling pathways in chordoma remain incompletely characterized. The aim of the present study was to delineate the global miRNA expression profile and associated signaling networks in chordoma. miRNA profiling was performed on chordoma and fetal notochord tissues. Differentially expressed miRNAs in chordoma were analyzed using microarrays with hierarchical clustering analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113170/screening-of-potential-therapy-targets-for-prostate-cancer-using-integrated-analysis-of-two-gene-expression-profiles
#16
Rui Zhao, Yao Wang, Muchun Zhang, Xinquan Gu, Weihua Wang, Jiufeng Tan, Xin Wei, Ning Jin
The aim of the present study was to analyze potential therapy targets for prostate cancer using integrated analysis of two gene expression profiles. First, gene expression profiles GSE38241 and GSE3933 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between prostate cancer and normal control samples were identified using the Linear Models for Microarray Data package. Pathway enrichment analysis of DEGs was performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112156/effects-of-lonomia-obliqua-venom-on-vascular-smooth-muscle-cells-contribution-of-nadph-oxidase-derived-reactive-oxygen-species
#17
João Alfredo Moraes, Genilson Rodrigues, Vany Nascimento-Silva, Mariana Renovato-Martins, Markus Berger, Jorge Almeida Guimarães, Christina Barja-Fidalgo
Envenomation caused by human contact with the caterpillar Lonomia is characterized by deleterious effects on coagulation and patency of blood vessels. The cellular effects induced by Lonomia obliqua venom highlights its capacity to activate endothelial cells, leading to a proinflammatory phenotype. Having more knowledge about the mechanisms involved in envenomation may contribute to better treatment. We aimed to evaluate the effects of Lonomia obliqua caterpillar bristle extract (LOCBE) on vascular smooth muscle cells (VSMC)...
November 7, 2017: Toxins
https://www.readbyqxmd.com/read/29104464/selective-killing-of-melanoma-cells-with-non-thermal-atmospheric-pressure-plasma-and-p-fak-antibody-conjugated-gold-nanoparticles
#18
Byul Bo Ra Choi, Jeong Hae Choi, Jin Woo Hong, Ki Won Song, Hae June Lee, Uk Kyu Kim, Gyoo Cheon Kim
Melanomas are fast growing high-mortality tumors, and specific treatments for melanomas are needed. Melanoma cells overexpress focal adhesion kinase (FAK) compared to normal keratinocytes, and we sought to exploit this difference to create a selectively lethal therapy. We combined gold nanoparticles (GNP) with antibodies targeting phosphorylated FAK (p-FAK). These conjugates (p-FAK-GNP) entered G361 melanoma cells and bound p-FAK. Treatment with p-FAK-GNP decreased the viability of G361 cells in a time dependent manner by inducing apoptosis...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29102081/phosphamide-containing-diphenylpyrimidine-analogues-pa-dppys-as-potent-focal-adhesion-kinase-fak-inhibitors-with-enhanced-activity-against-pancreatic-cancer-cell-lines
#19
He Liu, Bin Wu, Yang Ge, Jiaxin Huang, Shijie Song, Changyuan Wang, Jihong Yao, Kexin Liu, Yanxia Li, Yongming Li, Xiaodong Ma
A family of phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) were synthesized as potent focal adhesion kinase (FAK) inhibitors. The PA-DPPY derivatives could significantly inhibit the FAK enzymatic activity at concentrations lower than 10.69 nM. Among them, compounds 7a and 7e were two of the most active FAK inhibitors, possessing IC50 values of 4.25 nM and 4.65 nM, respectively. In particular, compound 7e also displayed strong activity against AsPC cell line, with an IC50 of 1.66 μM, but show low activity against the normal HPDE6-C7 cells (IC50 > 20 μM), indicating its low cell cytotoxicity...
September 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29101014/integrin-linked-kinase-a-new-actor-in-the-ageing-process
#20
Gemma Olmos, Susana López-Ongil, Maria Piedad Ruiz Torres
Integrin-linked kinase (ILK) is a protein located in focal adhesion complexes that is linked to the cytoplasmic domain of integrin receptors. Together with PINCH and parvin, ILK forms the IPP complex, which is associated with conserved intracellular signalling pathways and integrin regulation of the actin cytoskeleton. ILK plays an essential role in a wide variety of cellular functions, including cell migration, differentiation, survival, and division. The present review summarizes recent evidence, suggesting a new role for ILK in organismal ageing and cellular senescence, indicating that ILK is a key regulator of longevity and premature cellular senescence induced by extracellular stressors...
October 31, 2017: Experimental Gerontology
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