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https://www.readbyqxmd.com/read/28320610/carbon-monoxide-releasing-molecule-401-suppresses-polymorphonuclear-leukocyte-migratory-potential-by-modulating-f-actin-dynamics
#1
Ken Inoue, Eric K Patterson, Alfredo Capretta, Abdel R Lawendy, Douglas D Fraser, Gediminas Cepinskas
Carbon monoxide-releasing molecules (CORMs) suppress inflammation by reducing polymorphonuclear leukocyte (PMN) recruitment to the affected organs. We investigated modulation of PMN-endothelial cell adhesive interactions by water-soluble CORM-401 using an experimental model of endotoxemia in vitro. Human umbilical vein endothelial cells grown on laminar-flow perfusion channels were stimulated with 1 μg/mL lipopolysaccharide for 6 hours and perfused with 100 μmol/L CORM-401 (or inactive compound iCORM-401)-pretreated PMN for 5 minutes in the presence of 1...
March 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28301299/differential-role-for-pak1-and-pak4-during-the-invadopodia-lifecycle
#2
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Claire M Wells
PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZRho-GEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics...
March 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28288786/p21-activated-kinase-4-regulates-hif-1%C3%AE-translation-in-cancer-cells
#3
Hyunju Kim, Dustin J Woo, So Yeon Kim, Eun Gyeong Yang
The p21-activated kinases (Paks) interact with Rac/Cdc42 GTPases to regulate the actin cytoskeleton as well as various signaling pathways. Although activation of Paks in many human cancers is known to mediate cancer progression, the role of Pak proteins in hypoxia is poorly understood. In this study, we found that both Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-inducible factor-1α (HIF-1α) in hypoxia. We further discovered that Pak4 regulates HIF-1α translation via the Akt-mTOR-4E-BP1 pathway under hypoxic conditions...
March 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28288135/targeting-lyn-regulates-snail-family-shuttling-and-inhibits-metastasis
#4
D Thaper, S Vahid, K M Nip, I Moskalev, X Shan, S Frees, M E Roberts, K Ketola, K W Harder, C Gregory-Evans, J L Bishop, A Zoubeidi
The acquisition of an invasive phenotype by epithelial cells occurs through a loss of cellular adhesion and polarity, heralding a multistep process that leads to metastatic dissemination. Since its characterization in 1995, epithelial-mesenchymal transition (EMT) has been closely linked to the metastatic process. As a defining aspect of EMT, loss of cell adhesion through downregulation of E-cadherin is carried out by several transcriptional repressors; key among them the SNAI family of transcription factors...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28287395/p27-kip1-promotes-invadopodia-turnover-and-invasion-through-the-regulation-of-the-pak1-cortactin-pathway
#5
Pauline Jeannot, Ada Nowosad, Renaud T Perchey, Caroline Callot, Evangeline Bennana, Takanori Katsube, Patrick Mayeux, François Guillonneau, Stéphane Manenti, Arnaud Besson
p27(Kip1) (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity...
March 13, 2017: ELife
https://www.readbyqxmd.com/read/28278510/autocrine-vegf-and-il-8-promote-migration-via-src-vav2-rac1-pak1-signaling-in-human-umbilical-vein-endothelial-cells
#6
Li Ju, Zhiwen Zhou, Bo Jiang, Yue Lou, Xirong Guo
BACKGROUND/AIMS: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). METHODS: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs...
March 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28273460/agrin-as-a-mechanotransduction-signal-regulating-yap-through-the-hippo-pathway
#7
Sayan Chakraborty, Kizito Njah, Ajaybabu V Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28265680/indirubin-inhibits-the-migration-invasion-and-activation-of-fibroblast-like-synoviocytes-from-rheumatoid-arthritis-patients
#8
Mingcheng Huang, Lihui Wang, Shan Zeng, Qian Qiu, Yaoyao Zou, Maohua Shi, Hanshi Xu, Liuqin Liang
OBJECTIVES: To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs. METHODS: The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining...
March 6, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28252009/nicotine-facilitates-vsmc-dysfunction-through-a-mir-200b-rhogdia-cytoskeleton-module
#9
Dongli Liang, Zhaoxia Wang, Zhiqiang Yan, Shangwei Hou, Wangjie Xu, Lianyun Wang, Meisheng Shang, Zhongdong Qiao
Nicotine can induce the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs). We have previously shown that cytoskeletal proteins and RhoGDIA, a negative regulator of the Rho GTPase pathway, are involved in the nicotine-induced dysfunction of VSMCs. Here, we found that nicotine can activate the Rho GTPase pathway and induce the synthesis of the cytoskeletal proteins in VSMCs through the activation of intracellular downstream signaling pathways, including targets such as MYPT1, PAK1 and PI3K/AKT...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250131/measles-virus-enters-breast-and-colon-cancer-cell-lines-through-a-pvrl4-mediated-macropinocytosis-pathway
#10
Sebastien Delpeut, Gary Sisson, Karen M Black, Christopher D Richardson
Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease, but has emerged as a promising oncolytic platform. Previous studies of MeV entry have focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express MeV receptors, SLAM (Signaling Lymphocyte-Activating Molecule) and PVRL4 (Poliovirus Receptor-Like-4, nectin-4)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28249931/correction-pak1-is-a-novel-therapeutic-target-in-tyrosine-kinase-inhibitor-resistant-lung-adenocarcinoma-activated-by-the-pi3k-akt-signaling-regardless-of-egfr-mutation
#11
(no author information available yet)
No abstract text is available yet for this article.
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28202661/targeting-pak1
#12
REVIEW
Galina Semenova, Jonathan Chernoff
p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28186966/clinicopathological-signature-of-p21-activated-kinase-1-in-prostate-cancer-and-its-regulation-of-proliferation-and-autophagy-via-the-mtor-signaling-pathway
#13
Zhanyu Wang, Guojin Jia, Yan Li, Jikai Liu, Jinfang Luo, Jihong Zhang, Guoxiong Xu, Gang Chen
Prostate cancer (PCa) is one of the most common malignant tumors in men. The etiology and pathogenesis of PCa remain unclear. P21-activated kinase 1 (PAK1) is a member of a family of serine/threonine kinases and regulates cell growth and contributes to tumor invasion and metastasis. However, the association of PAK1 with PCa tumorigenesis and in particular with cell autophagy remains unknown. We found that the positive expression of PAK1 was significantly increased in PCa patients compared with BPH patients (P < 0...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#14
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDS) arise from a small population of disease initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in stem and progenitor numbers are also seen in a stage specific manner in human MDS samples as well as in murine models of the disease...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28155899/fingolimod-alters-the-transcriptome-profile-of-circulating-cd4-cells-in-multiple-sclerosis
#15
Jörg Friess, Michael Hecker, Luisa Roch, Dirk Koczan, Brit Fitzner, Ines Charlotte Angerer, Ina Schröder, Kristin Flechtner, Hans-Jürgen Thiesen, Alexander Winkelmann, Uwe Klaus Zettl
Multiple sclerosis is a demyelinating disease affecting the central nervous system. T cells are known to contribute to this immune-mediated condition. Fingolimod modulates sphingosine-1-phosphate receptors, thereby preventing the egress of lymphocytes, especially CCR7-expressing CD8+ and CD4+ T cells, from lymphoid tissues. Using Affymetrix Human Transcriptome Arrays (HTA 2.0), we performed a transcriptome profiling analysis of CD4+ cells obtained from the peripheral blood of patients with highly active relapsing-remitting multiple sclerosis...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28109008/inhibition-of-group-1-p21-activated-kinases-suppresses-pancreatic-stellate-cell-activation-and-increases-survival-of-mice-with-pancreatic-cancer
#16
Dannel Yeo, Phoebe Phillips, Graham S Baldwin, Hong He, Mehrdad Nikfarjam
Pancreatic cancer remains one of the most lethal of all solid tumors. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21-activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using the modified outgrowth method. The effect of inhibiting PAK1 with group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28099434/mlst-based-population-genetic-analysis-in-a-global-context-reveals-clonality-amongst-cryptococcus-neoformans-var-grubii-vni-isolates-from-hiv-patients-in-southeastern-brazil
#17
Kennio Ferreira-Paim, Leonardo Andrade-Silva, Fernanda M Fonseca, Thatiana B Ferreira, Delio J Mora, Juliana Andrade-Silva, Aziza Khan, Aiken Dao, Eduardo C Reis, Margarete T G Almeida, Andre Maltos, Virmondes R Junior, Luciana Trilles, Volker Rickerts, Ariya Chindamporn, Jane E Sykes, Massimo Cogliati, Kirsten Nielsen, Teun Boekhout, Matthew Fisher, June Kwon-Chung, David M Engelthaler, Marcia Lazéra, Wieland Meyer, Mario L Silva-Vergara
Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28098826/hair-growth-promoting-and-anticancer-effects-of-p21-activated-kinase-1-pak1-inhibitors-isolated-from-different-parts-of-alpinia-zerumbet
#18
Nozomi Taira, Binh Cao Quan Nguyen, Shinkichi Tawata
PAK1 (p21-activated kinase 1) is an emerging target for the treatment of hair loss (alopecia) and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia) in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG) and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%-180% and 132%-226%, respectively, at 10-100 μM...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28087248/corrigendum-to-git1-beta-pix-signaling-proteins-and-pak1-kinase-regulate-microtubule-nucleation-biochim-biophys-acta-1863-6pa-2016-1282-1297
#19
Markéta Černohorská, Vadym Sulimenko, Zuzana Hájková, Tetyana Sulimenko, Vladimíra Sládková, Stanislav Vinopal, Eduarda Dráberová, Pavel Dráber
No abstract text is available yet for this article.
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28055013/microrna-494-inhibits-breast-cancer-progression-by-directly-targeting-pak1
#20
Meng-Na Zhan, Xiao-Ting Yu, Jun Tang, Ci-Xiang Zhou, Chen-Long Wang, Qian-Qian Yin, Xiu-Feng Gong, Ming He, Jian-Rong He, Guo-Qiang Chen, Qian Zhao
MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro. Moreover, ectopic expression of miR-494 suppresses neoplasm initiation as well as pulmonary metastasis in vivo...
January 5, 2017: Cell Death & Disease
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