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https://www.readbyqxmd.com/read/28108732/fak-regulates-e-cadherin-expression-via-p-srcy416-p-erk1-2-p-stat3y705-and-ppar%C3%AE-mir-125b-stat3-signaling-pathway-in-b16f10-melanoma-cells
#1
Guoshun Pei, Yan Lan, Dianhua Chen, Lina Ji, Zi-Chun Hua
Focal adhesion kinase (FAK) is involved in tumor cell migration and metastasis. However, the underlying mechanism remains unclear. Here, we present a signaling pathway involved in the regulation of melanoma cell migration by FAK. We found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. The down-regulation of FAK inhibited the expression of p-SrcY416, p-ERK1/2, Stat3 and p-Stat3Y705, while promoted the expression of PPARγ, miR-125b and E-cadherin...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28108160/exposure-to-endosulfan-increases-endothelial-permeability-by-transcellular-and-paracellular-pathways-in-relation-to-cardiovascular-diseases
#2
Dan Xu, Tong Liu, Limei Lin, Shuai Li, Xiaoming Hang, Yeqing Sun
Exposure to environmental pollutants results in out-of-balance of vascular homeostasis. Endothelial dysfunction leads to a disruption of the endothelial permeability characteristics, associated with cardiovascular diseases. We previously reported that endosulfan could cause endothelial dysfunction, but the role of endosulfan in permeability of endothelial cells has been unexplored. To elucidate molecular mechanism of endosulfan-induced changes in endothelial permeability, human umbilical vein endothelial cells (HUVECs) were exposed to endosulfan, followed by endothelial permeability analysis...
January 17, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28104814/kon-tiki-perdido-enhances-ps2-integrin-adhesion-and-localizes-its-ligand-thrombospondin-in-the-myotendinous-junction
#3
J J Pérez-Moreno, A G Espina-Zambrano, C B García-Calderón, B Estrada
Cell-extracellular matrix adhesion is mediated by cell receptors, mainly integrins and transmembrane proteoglycans, which can functionally interact. How these receptors are regulated and coordinated is largely unknown and key to understand cell adhesion in development. We show that the conserved transmembrane proteoglycan Kon-tiki/Perdido (Kon) interacts with αPS2βPS integrin to mediate muscle-tendon adhesion. Double mutant embryos for kon and inflated show a synergistic increase in muscle detachment. Furthermore, Kon modulates αPS2βPS signaling at the muscle attachment, since P-Fak is reduced in kon mutants...
January 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28104102/inhibition-of-focal-adhesion-kinase-on-hepatic-stellate-cell-adhesion-and-migration
#4
Yan Wang, Junji Ma, Lei Chen, Xiao-Li Xie, Huiqing Jiang
OBJECTIVE: Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signals participate in the activation of HSCs. We evaluated the effect of FAK-related nonkinase (FRNK) on the adhesion and migration of HSCs. MATERIALS AND METHODS: Hepatic fibrosis was induced in Sprague-Dawley rats by means of bile duct ligation. Livers were harvested at 1, 2, 3 and 4 weeks after the ligation; livers of sham-operated animals were harvested at 4 weeks after ligation...
January 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28102310/coordinated-cell-motility-is-regulated-by-a-combination-of-lkb1-farnesylation-and-kinase-activity
#5
S Wilkinson, Y Hou, J T Zoine, J Saltz, C Zhang, Z Chen, L A D Cooper, A I Marcus
Cell motility requires the precise coordination of cell polarization, lamellipodia formation, adhesion, and force generation. LKB1 is a multi-functional serine/threonine kinase that associates with actin at the cellular leading edge of motile cells and suppresses FAK. We sought to understand how LKB1 coordinates these multiple events by systematically dissecting LKB1 protein domain function in combination with live cell imaging and computational approaches. We show that LKB1-actin colocalization is dependent upon LKB1 farnesylation leading to RhoA-ROCK-mediated stress fiber formation, but membrane dynamics is reliant on LKB1 kinase activity...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098914/role-of-mir-647-in-human-gastric-cancer-suppression
#6
Wenlong Cao, Weiyuan Wei, Zexu Zhan, Dongyi Xie, Yubo Xie, Qiang Xiao
MicroRNAs (miRNAs) regulate various oncogenes concomitantly, resulting in tumor suppression. They regulate proliferation and migration pathways in tumor development, suggesting a potential therapeutic role. In the present study, we found that miR-647 was markedly downregulated in gastric cancer (GC), and was significantly correlated with reduced tumor size and metastasis. In addition, miR-647 was also reduced in GC cell lines. Furthermore, overexpression of miR-647 in the GC cell lines inhibited cell proliferation, promoted cell cycle arrest at the G0/G1 phase and induced cell apoptosis...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098292/an-andrographolide-derivative-agp-26b-exhibiting-anti-angiogenic-activity-in-huvecs-and-zebrafish-via-blocking-the-vegfa-vegfr2-signaling-pathway
#7
Bin Huang, Yuran Peng, Jingjing Li, Shang Li, Yicheng Sun, Decai Wang, Binrui Yang, Judy Yuet-Wa Chan, Huidong Yu, George Pak-Heng Leung, Maggie Pui-Man Hoi, Guo-Chun Zhou, Simon Ming-Yuen Lee
The aim of this study is to investigate the anti-angiogenic properties of andrographolide derivatives AGP-26a (12β-isomer), AGP-26b (12α-isomer) and AGP-26 (4 : 1 mixture of AGP-26a and AGP-26b) in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) and the Tg(fli-1a:EGFP)y1 zebrafish model were used to identify the anti-angiogenic activities of AGP-26, AGP-26a, and AGP-26b. The results showed that AGP-26b exhibits the strongest inhibitory effect on VEGF-induced proliferation, migration, invasion and formation of capillary-like structures in HUVECs...
January 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28094806/plant-toxin-%C3%AE-odap-activates-integrin-%C3%AE-1-and-focal-adhesion-a-critical-pathway-to-cause-neurolathyrism
#8
Rui-Yue Tan, Geng-Yan Xing, Guang-Ming Zhou, Feng-Min Li, Wen-Tao Hu, Fernand Lambein, Jun-Lan Xiong, Sheng-Xiang Zhang, Hai-Yan Kong, Hao Zhu, Zhi-Xiao Li, You-Cai Xiong
Neurolathyrism is a unique neurodegeneration disease caused by β-N-oxalyl-L-α, β- diaminopropionic (β-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, β-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca(2+) from mitochondria to cellular matrix...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094782/cocaine-enhances-dc-to-t-cell-hiv-1-transmission-by-activating-dc-sign-larg-lsp1-complex-and-facilitating-infectious-synapse-formation
#9
Anil Prasad, Rutuja Kulkarni, Shuxian Jiang, Jerome E Groopman
DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated 'signalosome' complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092671/pde4d-promotes-fak-mediated-cell-invasion-in-braf-mutated-melanoma
#10
J Delyon, A Servy, F Laugier, J André, N Ortonne, M Battistella, S Mourah, A Bensussan, C Lebbé, N Dumaz
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088523/the-selective-cysteinyl-leukotriene-receptor-1-cyslt1r-antagonist-montelukast-regulates-extracellular-matrix-remodeling
#11
Jingli Peng, Hezheng Zhou, Guoping Kuang, Lilian Xie, Tao Tian, Ru Liu
Scar formation after filtration surgery of glaucoma is mainly caused by excessive synthesis of new extracellular matrix (ECM) and contraction of subconjunctival tissue mediated by human Tenon fibroblasts (HTFs) and the transforming growth factor (TGF-β1). Montelukast, a potent and specific cysteinyl leukotriene receptor 1 (cysLT1R) antagonist, is a licensed drug clinically used for the treatment of bronchial asthma. In this study, we investigated the effects of montelukast on the contractility of HTFs cultured in a three-dimensional collagen gel...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28077433/osteoprotegerin-disruption-attenuates-hysu-induced-pulmonary-hypertension-through-integrin-%C3%AE-v%C3%AE-3-fak-akt-pathway-suppression
#12
Daile Jia, Qian Zhu, Huan Liu, Caojian Zuo, Yuhu He, Guilin Chen, Ankang Lu
BACKGROUND: Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). Clinical studies have suggested a correlation between osteoprotegerin serum levels and PAH severity. Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28076322/aeroallergen-der-p-2-promotes-motility-of-human-non-small-cell-lung-cancer-cells-via-toll-like-receptor-mediated-up-regulation-of-urokinase-type-plasminogen-activator-and-integrin-focal-adhesion-kinase-signaling
#13
Chun-Hsiang Lin, Hui-Han Lin, Cheng-Yi Kuo, Shao-Hsuan Kao
House dust mite (HDM) allergens are one of the major causes leading to respiratory hypersensitiveness and airway remodeling. Here we hypothesized that a major HDM allergen Der p 2 could increase cell motility and invasiveness of non-small cell lung cancer (NSCLC) cells. Our results showed that low dose (1 and 3 μg/mL) recombinant Der p 2 protein (DP2) enhanced the migration and invasiveness of human NSCLC cell A549, H1299 and CL1-5, but nonsignificantly altered their growth. Further investigation revealed that integrin αV level was increased and its downstream signaling including focal adhesion kinase (FAK) and paxillin were activated in A549 cells exposed to DP2...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075447/anti-metastatic-effect-of-rhodomyrtone-from-rhodomyrtus-tomentosa-on-human-skin-cancer-cells
#14
Malatee Tayeh, Sirinun Nilwarangoon, Wilawan Mahabusarakum, Ramida Watanapokasin
This study focused on the inhibitory effect of rhodomyrtone, a bioactive compound isolated from the leaves of Rhodomyrtus tomentosa (Aiton) Hassk., on cancer metastasis in epidermoid carcinoma A431 cells and on the verification of the underlying related molecular mechanisms of this event. We demonstrated that rhodomyrtone at the subcytotoxic concentration (0.5 and 1.5 µg/ml) exhibited pronounced inhibition of cancer metastasis by reducing cell migration, cell adhesive ability and cell invasion of A431 cells in a dose-dependent manner...
January 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28072455/src-and-phospho-fak-kinases-are-activated-by-allopregnanolone-promoting-schwann-cells-motility-morphology-and-myelination
#15
Simona Melfi, Maria Magdalena Montt Guevara, Veronica Bonalume, Massimiliano Ruscica, Alessandra Colciago, Tommaso Simoncini, Valerio Magnaghi
Schwann cells' (SCs) development and maturation require coordinate and complementary interaction among several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs' fate, participating in regulation of SC adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SC motility and proliferation, which are crucial processes for nerve development, maturation and regeneration...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28069919/calpain-mediated-proteolysis-of-talin-and-fak-regulates-adhesion-dynamics-necessary-for-axon-guidance
#16
Patrick C Kerstein, Kevin M Patel, Timothy M Gomez
: Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca(2+)) is an essential signal for axon guidance that mediates opposing affects on growth cone motility. The diverse effects of Ca(2+) arise from the precise localization of Ca(2+) signals into microdomains containing specific Ca(2+) effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca(2+) signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069687/adaptive-resistance-of-melanoma-cells-to-raf-inhibition-via-reversible-induction-of-a-slowly-dividing-de-differentiated-state
#17
Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia-Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, Peter K Sorger
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly...
January 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28069443/the-cyclic-amp-phosphodiesterase-4d5-pde4d5-receptor-for-activated-c-kinase-1-rack1-signalling-complex-as-a-sensor-of-the-extracellular-nano-environment
#18
REVIEW
Stephen J Yarwood, Euan Parnell, Rebecca J Bird
The cyclic AMP and protein kinase C (PKC) signalling pathways regulate a wide range of cellular processes that require tight control, including cell proliferation and differentiation, metabolism and inflammation. The identification of a protein complex formed by receptor for activated C kinase 1 (RACK1), a scaffold protein for protein kinase C (PKC), and the cyclic AMP-specific phosphodiesterase, PDE4D5, demonstrates a potential mechanism for crosstalk between these two signalling routes. Indeed, RACK1-bound PDE4D5 is activated by PKCα, providing a route through which the PKC pathway can control cellular cyclic AMP levels...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28068967/enterolactone-alters-fak-src-signaling-and-suppresses-migration-and-invasion-of-lung-cancer-cell-lines
#19
Shireen Chikara, Kaitlin Lindsey, Pawel Borowicz, Melpo Christofidou-Solomidou, Katie M Reindl
BACKGROUND: Systemic toxicity of chemotherapeutic agents and the challenges associated with targeting metastatic tumors are limiting factors for current lung cancer therapeutic approaches. To address these issues, plant-derived bioactive components have been investigated for their anti-cancer properties because many of these agents are non-toxic to healthy tissues. Enterolactone (EL) is a flaxseed-derived mammalian lignan that has demonstrated anti-migratory properties for various cancers, but EL has not been investigated in the context of lung cancer, and its anticancer mechanisms are ill-defined...
January 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28068557/cordycepin-inhibits-migration-of-human-glioblastoma-cells-by-affecting-lysosomal-degradation-and-protein-phosphatase-activation
#20
Dueng-Yuan Hueng, Ching-Hsuan Hsieh, Yu-Chen Cheng, Wen-Chiuan Tsai, Ying Chen
Cordycepin, a nucleoside-derivative-isolated form Cordyceps militaris, has been reported to suppress tumor cell proliferation and cause apoptosis. This study investigates the effect of cordycepin on the migration of human glioblastoma cells. Cordycepin suppressed the migration of the human glioblastoma cell lines U87MG and LN229 in transwell and wound healing assays. Cordycepin decreased protein expression of integrin α1, focal adhesion kinase (FAK), p-FAK, paxillin and p-paxillin. The lysosomal inhibitor NH4Cl blocked the ability of cordycepin to inhibit focal adhesion protein expression and glioma cell migration...
December 29, 2016: Journal of Nutritional Biochemistry
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