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https://www.readbyqxmd.com/read/28535002/hsa-mir-485-5p-reverses-epithelial-to-mesenchymal-transition-and-promotes-cisplatin-induced-cell-death-by-targeting-pak1-in-oral-tongue-squamous-cell-carcinoma
#1
Xiu-Juan Lin, Chang-Li He, Ting Sun, Xue-Jing Duan, Yi Sun, Shi-Jiang Xiong
Oral squamous cell carcinoma (OSCC) is currently a highly prevalent disease worldwide. Cisplatin (CDDP) is widely used for the chemotherapy of OSCC. Yet, the molecular mechanisms responsible for cisplatin resistance have not been fully elucidated. In this study, we showed that overexpression of p21 (RAC1) activated kinase 1 (PAK1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells. Emerging evidence indicates a strong link between resistance to therapy and the induction of EMT in cancer...
May 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28533545/treatment-effects-of-the-traditional-chinese-medicine-shenks-in-bleomycin-induced-lung-fibrosis-through-regulation-of-tgf-beta-smad3-signaling-and-oxidative-stress
#2
Haiyan Chu, Ying Shi, Shuai Jiang, Qicheng Zhong, Yongqiang Zhao, Qingmei Liu, Yanyun Ma, Xiangguang Shi, Weifeng Ding, Xiaodong Zhou, Jimin Cui, Li Jin, Gang Guo, Jiucun Wang
Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28531799/numb-had-anti-tumor-effects-in-prostatic-cancer
#3
Ji Sun, Kai Wang, Jingfei Teng, Yufu Yu, Runmiao Hua, Haiyong Zhou, Dachuan Zhong, Yi Fan
AIM: The aim of this study was to explain the Numb anti-cancer effects in the prostatic cancer. METHODS: Collecting the 20 prostatic cancer patients and analyzing the correlation between Numb and Glease score. Transfection Numb into DU-145 and PC-3 cells, measuring the proliferation rate of difference groups by MTT assay, evaluating the cell apoptosis and cell cycle of difference group by Flow cytometry; measuring the invasion and migration abilities by transwell and wound healing assays...
May 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528507/mertk-does-not-mediate-phagocytosis-of-staphylococcus-aureus-but-attenuates-inflammation-induced-by-staphylococcal-lipoteichoic-acid-through-blocking-nf-%C3%AE%C2%BAb-activation
#4
Bing Zhang, Huimei Wu, Lei Fang, Peishan Ding, Ke Xu, Qingbin Yang, Rongyu Liu
Mer receptor tyrosine kinase (MerTK) expressed in macrophages is essential for phagocytosis of apoptotic cells. Here, we investigate whether MerTK is involved in the phagocytosis of Staphylococcus aureus (S. aureus) and regulation of staphylococcal lipoteichoic acid (LTA)-induced inflammatory response in macrophages. We found that stimulating RAW264.7 macrophages with S. aureus activated multiple signaling pathways including toll-like receptor 2 (TLR2), scavenger receptor A (SR-A), and MerTK. Meanwhile, S. aureus stimulation also induced activation of proteins focal adhesion kinase (FAK) and Rac1, which are related to phagocytosis...
May 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#5
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28527916/cadmium-stimulates-metastasis-associated-phenotype-in-triple-negative-breast-cancer-cells-through-integrin-and-%C3%AE-catenin-signaling
#6
Zhengxi Wei, Zahir A Shaikh
Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1μM Cd increased cell spreading and cell migration...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#7
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28520772/the-chicken-embryo-as-an-efficient-model-to-test-the-function-of-muscle-fusion-genes-in-amniotes
#8
Daniel Sieiro, Nadège Véron, Christophe Marcelle
The fusion of myoblasts into multinucleated myotubes is a crucial step of muscle growth during development and of muscle repair in the adult. While multiple genes were shown to play a role in this process, a vertebrate model where novel candidates can be tested and analyzed at high throughput and relative ease has been lacking. Here, we show that the early chicken embryo is a fast and robust model in which functional testing of muscle fusion candidate genes can be performed. We have used known modulators of muscle fusion, Rac1 and Cdc42, along with the in vivo electroporation of integrated, inducible vectors, to show that the chicken embryo is a suitable model in which their function can be tested and quantified...
2017: PloS One
https://www.readbyqxmd.com/read/28515142/flow-induced-endothelial-cell-alignment-requires-the-rhogef-trio-as-a-scaffold-protein-to-polarize-active-rac1-distribution
#9
Jeffrey Kroon, Niels Heemskerk, Martin J T Kalsbeek, Vivian de Waard, Jos van Rijssel, Jaap D van Buul
Endothelial cells line the lumen of the vessel wall and are exposed to flow. In linear parts of the vessel, the endothelial cells experience laminar flow, resulting in endothelial cell alignment in the direction of flow, thereby protecting the vessel wall from inflammation and permeability. In order for endothelial cells to align, they undergo rapid remodeling of the actin cytoskeleton by local activation of the small GTPase Rac1. However, if sustained and local activation of Rac1 is required for long-term flow-induced cell alignment is not clear...
May 17, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28513465/the-role-of-srsf1-in-cancer
#10
Elżbieta Sokół, Joanna Bogusławska, Agnieszka Piekiełko-Witkowska
SRSF1 jest wielofunkcyjnym białkiem biorącym udział w procesach związanych z metabolizmem RNA. Następstwem zaburzeń ekspresji SRSF1, obserwowanych w wielu typach nowotworów, są nieprawidłowości w składaniu pre-mRNA, zmiany stabilności transkryptów i poziomu translacji onkogenów oraz genów supresorowych. Regulując różnicowe składanie transkryptów genów CCND1, RAC1, KLF6, BCL2L1, MCL1 oraz CASP9, SRSF1 indukuje zmiany w cyklu komórkowym, proliferacji i apoptozie. Czynnik SRSF1 wpływa także na angiogenezę nowotworową i przerzutowanie, m...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28512254/catecholamines-facilitate-vegf-dependent-angiogenesis-via-%C3%AE-2-adrenoceptor-induced-epac1-and-pka-activation
#11
Jaspal Garg, Yu-Xi Feng, Sepp R Jansen, Julian Friedrich, Frank Lezoualc'h, Martina Schmidt, Thomas Wieland
Chronic stress has been associated with the progression of cancer and antagonists for β-adrenoceptors (βAR) are regarded as therapeutic option. As they are also used to treat hemangiomas as well as retinopathy of prematurity, a role of endothelial β2AR in angiogenesis can be envisioned. We therefore investigated the role of β2AR-induced cAMP formation by analyzing the role of the cAMP effector molecules exchange factor directly activated by cAMP 1 (Epac1) and protein kinase A (PKA) in endothelial cells (EC)...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512198/novel-role-of-rac-mid1-signaling-in-medial-cerebellar-development
#12
Takashi Nakamura, Takehiko Ueyama, Yuzuru Ninoyu, Hirofumi Sakaguchi, Narantsog Choijookhuu, Yoshitaka Hishikawa, Hiroshi Kiyonari, Masaaki Kohta, Mizuho Sakahara, Ivan de Curtis, Eiji Kohmura, Yasuo Hisa, Atsu Aiba, Naoaki Saito
Rac signaling impacts a relatively large number of downstream targets; however, few studies have established an association between Rac pathways and pathological conditions. In the present study, we generated mice with double knockout of Rac1 and Rac3 (Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) ) in cerebellar granule neurons (CGNs). We observed impaired tangential migration at E16.5, as well as numerous apoptotic CGNs at the deepest layer of the external granule layer (EGL) in the medial cerebellum of Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) mice at P8...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28507287/integrin-beta8-itgb8-activates-vav-rac1-signaling-via-fak-in-the-acquisition-of-endometrial-epithelial-cell-receptivity-for-blastocyst-implantation
#13
Vijay Kumar, Upendra Kumar Soni, Vineet Kumar Maurya, Kiran Singh, Rajesh Kumar Jha
Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28502648/control-of-astrocyte-morphology-by-rho-gtpases
#14
REVIEW
Andre Zeug, Franziska E Müller, Stefanie Anders, Michel K Herde, Daniel Minge, Evgeni Ponimaskin, Christian Henneberger
Astrocytes modulate and support neuronal and synapse function via numerous mechanisms that often rely on diffusion of signalling molecules, ions or metabolites through extracellular space. As a consequence, the spatial arrangement and the distance between astrocyte processes and neuronal structures is of functional importance. Likewise, changes of astrocyte structure will affect the ability of astrocytes to interact with neurons. In contrast to neurons, where rapid morphology changes are critically involved in many aspects of physiological brain function, a role of astrocyte restructuring in brain physiology is only beginning to emerge...
May 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28499439/the-role-of-tgf-%C3%AE-and-its-crosstalk-with-rac1-rac1b-signaling-in-breast-and-pancreas-carcinoma
#15
REVIEW
Catharina Melzer, Ralf Hass, Juliane von der Ohe, Hendrik Lehnert, Hendrik Ungefroren
This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers...
May 12, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28498728/a-family-affair-a-ral-exocyst-centered-network-links-ras-rac-rho-signaling-to-control-cell-migration
#16
Giulia Zago, Marco Biondini, Jacques Camonis, Maria Carla Parrini
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation...
May 12, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489964/specific-activation-of-plekhg2-induced-serum-response-element-dependent-gene-transcription-by-four-and-a-half-lim-domains-fhl-1-but-not-fhl2-or-fhl3
#17
Masashi Nishikawa, Katsuya Sato, Shun Nakano, Hisashi Yamakawa, Takahiro Nagase, Hiroshi Ueda
PLEKHG2 is a Gβγ- and Gαs-dependent guanine nucleotide exchange factor for Rac1 and Cdc42 small GTPases and has been shown to mediate signaling pathways such as those for actin cytoskeletal reorganization and serum response element (SRE)-dependent gene transcription. We have shown that the four-and-a-half LIM domains (FHL) 1 acts as a positive regulator of PLEKHG2. Here, we evaluated the other FHL family members and found that the FHL1A specifically regulate the PLEKHG2 activity. Moreover, FHL1A further enhanced Gβγ- and PLEKHG2-induced SRE-dependent gene transcription, whereas FHL1A partially restored the attenuated PLEKHG2-induced SRE-dependent gene transcription by Gαs...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28487945/nox4-is-involved-in-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-notch-pathway
#18
Min Yao, Feng Gao, Xiaomeng Wang, Yonghong Shi, Shuxia Liu, Huijun Duan
It has previously been demonstrated that nicotinamide adenine dinucleotide phosphate‑oxidase (NADPH) oxidase 4 (Nox4), is important in the pathogenesis of diabetic nephropathy (DN), however the exact mechanisms remain to be elucidated. The present study aimed to examine the effect of Nox4 on the alteration of the Notch pathway and cell apoptosis in the renal tubular epithelial cell line, HKC, under conditions of high glucose (HG; 30 mmol/l glucose). Nox4 and the Notch pathway were inhibited by N‑acetylcysteine (NAC), diphenylene iodonium (DPI) or γ‑secretase inhibitor (DAPT)...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487380/egfr-signals-through-a-dock180-mlk3-axis-to-drive-glioblastoma-cell-invasion
#19
Sean Misek, Jian Chen, Laura Schroeder, Chotirat Rattanasinchai, Ashley Sample, Jann N Sarkaria, Kathleen A Gallo
A hallmark of glioblastoma (GBM) tumors is their highly invasive behavior. Tumor dissemination into surrounding brain tissue is responsible for incomplete surgical resection, and subsequent tumor recurrence. Identification of targets that control GBM cell dissemination is critical for developing effective therapies to treat GBM. A majority of GBM tumors have dysregulated EGFR signaling, due most frequently to EGFR amplification or the presence of a constitutively active EGFRvIII mutant. Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that can activate multiple MAPK pathways...
May 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28484055/endothelial-cd2ap-binds-the-receptor-icam-1-to-control-mechanosignaling-leukocyte-adhesion-and-the-route-of-leukocyte-diapedesis-in-vitro
#20
Antje Schaefer, Trynette J van Duijn, Jisca Majolee, Keith Burridge, Peter L Hordijk
Inflammation is driven by excessive transmigration (diapedesis) of leukocytes from the blood to the tissue across the endothelial cell monolayer that lines blood vessels. Leukocyte adhesion, crawling, and transmigration are regulated by clustering of the endothelial mechanosensitive receptor intercellular adhesion molecule-1 (ICAM-1). Whereas several proteins are known to promote ICAM-1 function, the molecular mechanisms that limit ICAM-1-mediated adhesion to prevent excessive leukocyte transmigration remain unknown...
May 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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