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PAK1

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https://www.readbyqxmd.com/read/27920252/group-i-paks-promote-skeletal-myoblast-differentiation-in-vivo-and-in-vitro
#1
Giselle A Joseph, Min Lu, Maria Radu, Jennifer K Lee, Steven J Burden, Jonathan Chernoff, Robert S Krauss
Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks, Pak1 and Pak2, are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation, and involves the cadherin co-receptor Cdo with its downstream effector, Cdc42...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27913610/whole-exome-sequencing-of-thymic-neuroendocrine-tumor-with-ectopic-acth-syndrome
#2
Yanli Li, Ying Peng, Xiuli Jiang, Yulong Cheng, Weiwei Zhou, Tingwei Su, Jing Xie, Xu Zhong, Dalong Song, Luming Wu, Liwen Fan, Min Li, Jie Hong, Weiqing Wang, Guang Ning, Yanan Cao
OBJECTIVE: Thymic neuroendocrine tumor is the second-most prevalent cause of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), which is a rare disease characterized by ectopic ACTH oversecretion from nonpituitary tumors. However, the genetic abnormalities of thymic neuroendocrine tumors with EAS remain largely unknown. We aim to elucidate the genetic abnormalities and identify the somatic mutations of potential tumor-related genes of thymic neuroendocrine tumors with EAS by whole exome sequencing...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27910850/the-guanine-nucleotide-exchange-factor-net1-facilitates-the-specification-of-dorsal-cell-fates-in-zebrafish-embryos-by-promoting-maternal-%C3%AE-catenin-activation
#3
Shi Wei, Miaomiao Dai, Zhaoting Liu, Yuanqing Ma, Hanqiao Shang, Yu Cao, Qiang Wang
Wnt/β-catenin signaling is essential for the initiation of dorsal-ventral patterning during vertebrate embryogenesis. Maternal β-catenin accumulates in dorsal marginal nuclei during cleavage stages, but its critical target genes essential for dorsalization are silent until mid-blastula transition (MBT). Here, we find that zebrafish net1, a guanine nucleotide exchange factor, is specifically expressed in dorsal marginal blastomeres after MBT, and acts as a zygotic factor to promote the specification of dorsal cell fates...
December 2, 2016: Cell Research
https://www.readbyqxmd.com/read/27889630/1-2-3-triazolyl-ester-of-ketorolac-a-click-chemistry-based-highly-potent-pak1-blocking-cancer-killer
#4
Binh Cao Quan Nguyen, Hideaki Takahashi, Yoshihiro Uto, M D Shahinozzaman, Shinkichi Tawata, Hiroshi Maruta
An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC50 against the growth of human cancer cells such as A549 is around 13 μM)...
November 20, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27889228/cardioprotective-effect-of-vitex-negundo-on-isoproterenol-induced-myocardial-necrosis-in-wistar-rats-a-dual-approach-study
#5
E Maruthi Prasad, Ramgopal Mopuri, Md Shahidul Islam, Lakshmi Devi Kodidhela
Cardiovascular diseases (CVDs) are becoming the major cause of deaths worldwide, and their treatment demands novel therapeutic strategies. In this connection, we have identified p21 activated kinase 1 (PAK1) as a novel therapeutic target for the treatment of myocardial infarction (MI), where its expression is decreased when MI is induced with isoproterenol (ISO), which was brought back normal with pretreatment of Vitex negundo leaf ethanolic extract (VNE). These results were also supported by histopathological studies, cardiac markers, antioxidants, and inflammatory cytokines (NF-κB and IL-1β)...
November 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27885255/tfap2c-mediated-upregulation-of-tgfbr1-promotes-lung-tumorigenesis-and-epithelial-mesenchymal-transition
#6
Wanyeon Kim, EunGi Kim, Sungmin Lee, Daehoon Kim, Jahyun Chun, Kang Hyun Park, HyeSook Youn, BuHyun Youn
TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#7
Lei Tan, Yuqiang Zhang, Yuan Zhan, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao, Chan Ding
Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852389/-expression-of-pak1-in-bladder-cancer-and-its-influence-on-invasion-of-bladder-cancer-cells
#8
K Huang, G Chen, Y Li, J K Liu, Z Y Wang, G C Zhou
Objective: To investigate the expression of p21-activated kinase 1 (PAK1) in bladder cancer and its biological influence on invasion ability of bladder cancer cells. Methods: A total of 54 paraffin-embedded bladder cancer tissue samples and 12 normal bladder tissue specimens were retrieved in Jinshan Hospital Affiliated to Fudan University between January 2009 and December 2012. The expression of PAK1 in these tissues was detected by immunohistochemical staining. The PAK1 mRNA and protein levels were measured in bladder cancer cell lines and human normal bladder epithelial cell line using real-time, fluorescence-based quantitative polymerase chain reaction (RT-PCR) and Western blot, respectively...
November 1, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27845911/deciphering-the-link-between-pi3k-and-pak-an-opportunity-to-target-key-pathways-in-pancreatic-cancer
#9
REVIEW
Kiruthikah Thillai, Hoyin Lam, Debashis Sarker, Claire M Wells
The development of personalised therapies has ushered in a new and exciting era of cancer treatment for a variety of solid malignancies. Yet pancreatic ductal adenocarcinoma (PDAC) has failed to benefit from this paradigm shift, remaining notoriously refractory to targeted therapies. Chemotherapy is the cornerstone of management but can offer only modest survival benefits of a few months with 5-year survival rates rarely exceeding 3%. Despite these disappointing statistics, significant strides have been made towards understanding the complex biology of pancreatic cancer, with deep genomic sequencing identifying novel genetic aberrations and key signalling pathways...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831589/the-anti-inflammatory-vasostatin-2-attenuates-atherosclerosis-in-apoe-mice-and-inhibits-monocyte-macrophage-recruitment
#10
Weixin Xiong, Xiaoqun Wang, Daopeng Dai, Bao Zhang, Lin Lu, Rong Tao
We showed previously that reduced level of vasostatin-2 (VS-2) correlates to the presence and severity of coronary artery disease. In this study, we aimed to figure out the role of chromogranin A (CGA) derived VS-2 in the development of atherosclerosis and monocyte/macrophage recruitment. Apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat diet exhibited attenuated lesion size by 65 % and 41 % in En face and aortic root Oil red O staining, MOMA-2 positive area by 64 %, respectively, in VS-2 treatment group compared with PBS group...
November 10, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27821782/rac1-rhoa-antagonism-defines-cell-to-cell-heterogeneity-during-epidermal-morphogenesis-in-nematodes
#11
Emmanuel Martin, Marie-Hélène Ouellette, Sarah Jenna
The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27818180/rac1-mediated-dna-damage-and-inflammation-promote-nf2-tumorigenesis-but-also-limit-cell-cycle-progression
#12
Yuhao Shi, Saumya R Bollam, Shannon M White, Sean Z Laughlin, Garrett T Graham, Mandheer Wadhwa, Hengye Chen, Chan Nguyen, Jeremie Vitte, Marco Giovannini, Jeffery Toretsky, Chunling Yi
Merlin encoded by the Nf2 gene is a bona fide tumor suppressor that has been implicated in regulation of both the Hippo-Yap and Rac1-Pak1 pathways. Using genetically engineered murine liver models, we show that co-deletion of Rac1 with Nf2 blocks tumor initiation but paradoxically exacerbates hepatomegaly induced by Nf2 loss, which can be suppressed either by treatment with pro-oxidants or by co-deletion of Yap. Our results suggest that while Yap acts as the central driver of proliferation during Nf2 tumorigenesis, Rac1 primarily functions as an inflammation switch by inducing reactive oxygen species that, on one hand, induce nuclear factor κB signaling and expression of inflammatory cytokines, and on the other activate p53 checkpoint and senescence programs dampening the cyclin D1-pRb-E2F1 pathway...
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27776471/reflecting-back-to-bring-nitric-oxide-research-to-the-laboratory
#13
Rakesh Kumar
Professor Ferid Murad has been a remarkable colleague and a mentor. During our very first meeting, he not only shared unresolved puzzles in Nitric Oxide (NO) research but also listened to my questions pointing to protein nitration and nitrosylation. This was start of a new avenue in my laboratory involving protein nitration, inducible nitric oxide synthase and nitrite production in the context of signaling and gene expression in cancer cells. Dynamic changes in the cytoskeleton remodeling in response to the cell membrane generated signals are regulated by p21-activated kinase 1 (PAK1) which also feed into microtubules (MT) dynamic via phosphorylating Tubulin Cofactor B (CoB) on serine 65 and serine 128...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27765920/pak4-suppresses-pdz-rhogef-activity-to-drive-invadopodia-maturation-in-melanoma-cells
#14
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Simon M Ameer-Beg, Jenny L C Geh, Ciaran Healy, Alistair D MacKenzie Ross, Maddy Parsons, Frank O Nestle, Katie E Lacy, Claire M Wells
Cancer cells are thought to use actin rich invadopodia to facilitate matrix degradation. Formation and maturation of invadopodia requires the co-ordained activity of Rho-GTPases, however the molecular mechanisms that underlie the invadopodia lifecycle are not fully elucidated. Previous work has suggested a formation and disassembly role for Rho family effector p-21 activated kinase 1 (PAK1) however, related family member PAK4 has not been explored. Systematic analysis of isoform specific depletion using in vitro and in vivo invasion assays revealed there are differential invadopodia-associated functions...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27760566/miip-remodels-rac1-mediated-cytoskeleton-structure-in-suppression-of-endometrial-cancer-metastasis
#15
Yingmei Wang, Limei Hu, Ping Ji, Fei Teng, Wenyan Tian, Yuexin Liu, David Cogdell, Jinsong Liu, Anil K Sood, Russell Broaddus, Fengxia Xue, Wei Zhang
BACKGROUND: Endometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP) gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. METHODS: Immunohistochemistry was used to measure MIIP expression in normal and EC tissue...
October 19, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27747949/seasonal-gene-expression-in-a-migratory-songbird
#16
Rachel A Johnston, Kristina L Paxton, Frank R Moore, Robert K Wayne, Thomas B Smith
The annual migration of a bird can involve thousands of kilometres of nonstop flight, requiring accurately timed seasonal changes in physiology and behaviour. Understanding the molecular mechanisms controlling this endogenous programme can provide functional and evolutionary insights into the circannual biological clock and the potential of migratory species to adapt to changing environments. Under naturally timed photoperiod conditions, we maintained captive Swainson's thrushes (Catharus ustulatus) and performed RNA sequencing (RNA-Seq) of the ventral hypothalamus and optic chiasma to evaluate transcriptome-wide gene expression changes of individuals in migratory condition...
November 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27746419/the-serum-pdgf-dependent-melanogenic-role-of-the-minute-level-of-the-oncogenic-kinase-pak1-in-melanoma-cells-proven-by-the-highly-sensitive-kinase-assay
#17
Pham Thi Be Tu, Binh Cao Quan Nguyen, Shinkichi Tawata, Cheong-Yong Yun, Eung Gook Kim, Hiroshi Maruta
We previously demonstrated that the oncogenic kinase PAK4, which both melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-ATP-Glo) kinase assay, we investigated the melanogenic potential of another oncogenic kinase PAK1, which melanoma (B16F10) cells express only at a very minute level. After transfecting melanoma cells with PAK1-shRNA for silencing PAK1 gene, melanin content, tyrosinase activity, and kinase activity of PAK1 were compared between the wild-type and transfectants...
October 17, 2016: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/27740936/reduced-pak1-activity-sensitizes-fa-brca-proficient-breast-cancer-cells-to-parp-inhibition
#18
Olga Villamar Cruz, Tatiana Y Prudnikova, Daniela Araiza-Olivera, Carlos Perez-Plasencia, Neil Johnson, Andrea J Bernhardy, Michael Slifker, Catherine Renner, Jonathan Chernoff, Luis E Arias-Romero
Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27739327/activity-of-caffeic-acid-phenethyl-ester-in-caenorhabditis-elegans
#19
Jeffrey J Coleman, Tomomi Komura, Julia Munro, Michael P Wu, Rakhee R Busanelli, Angela N Koehler, Méryl Thomas, Florence F Wagner, Edward B Holson, Eleftherios Mylonakis
AIM: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. RESULTS: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability...
October 14, 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27713506/pak1-confers-chemoresistance-and-poor-outcome-in-non-small-cell-lung-cancer-via-%C3%AE-catenin-mediated-stemness
#20
Ming-Jenn Chen, De-Wei Wu, Yao-Chen Wang, Chi-Yi Chen, Huei Lee
PAK1 confers resistance to the estrogen antagonist tamoxifen in breast cancer. However, a role for PAK1 remains to be elucidated for chemoresistance and prognosis in non-small cell lung cancer (NSCLC). We provide evidence that PAK1 confers cisplatin resistance by increasing β-catenin expression through ERK/GSK3β signaling. The increased β-catenin expression promotes sphere cell formation and expression of stemness markers and this β-catenin-induced stemness is responsible for PAK1-mediated cisplatin resistance...
October 7, 2016: Scientific Reports
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