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https://www.readbyqxmd.com/read/27926479/decline-in-arylsulfatase-b-leads-to-increased-invasiveness-of-melanoma-cells
#1
Sumit Bhattacharyya, Leo Feferman, Kaoru Terai, Arkadiusz Z Dudek, Joanne K Tobacman
Arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) is reduced in several malignancies, but levels in melanoma have not been investigated previously. Experiments were performed in melanoma cell lines to determine ARSB activity and impact on melanoma invasiveness. ARSB activity was reduced ~50% in melanoma cells compared to normal melanocytes. Silencing ARSB significantly increased the mRNA expression of chondroitin sulfate proteoglycan(CSPG)4 and pro-matrix metalloproteinase(MMP)-2, known mediators of melanoma progression...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894814/tanshinone-iia-induced-cell-death-via-mir30b-p53-ptpn11-shp2-signaling-pathway-in-human-hepatocellular-carcinoma-cells
#2
Xuanqi Ren, Cui Wang, Binbin Xie, Linfeng Hu, Hui Chai, Lei Ding, Lihua Tang, Yongliang Xia, Xiaobing Dou
Tanshinone IIA, a multi-pharmaceutical compound from traditional Chinese herb, has been reported to have anti-hepatocarcinomic (HCC) properties through cell death induction. Apart from the typical p53-dependent pathway, mechanisms of the anti-carcinogenic role of Tanshinone remain scarce. In an effort to explore the mechanism behind Tanshinone IIA, we detected the upstream of the p53 and the potential novel pathway. Tanshinone IIA dose-dependently initiated HepG2 cell apoptosis and cell cycle arrest at the G1 checkpoint...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27876799/irs4-induces-mammary-tumorigenesis-and-confers-resistance-to-her2-targeted-therapy-through-constitutive-pi3k-akt-pathway-hyperactivation
#3
Gerjon J Ikink, Mandy Boer, Elvira R M Bakker, John Hilkens
In search of oncogenic drivers and mechanisms affecting therapy resistance in breast cancer, we identified Irs4, a poorly studied member of the insulin receptor substrate (IRS) family, as a mammary oncogene by insertional mutagenesis. Whereas normally silent in the postnatal mammary gland, IRS4 is found to be highly expressed in a subset of breast cancers. We show that Irs4 expression in mammary epithelial cells induces constitutive PI3K/AKT pathway hyperactivation, insulin/IGF1-independent cell proliferation, anchorage-independent growth and in vivo tumorigenesis...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27864293/expressions-of-the-caga-protein-and-caga-signaling-molecules-predict-h-pylori-dependence-of-early-stage-gastric-dlbcl
#4
Sung-Hsin Kuo, Li-Tzong Chen, Chung-Wu Lin, Kun-Huei Yeh, Chia-Tung Shun, Yi-Shin Tzeng, Jyh-Ming Liou, Ming-Shiang Wu, Ping-Ning Hsu, Ann-Lii Cheng
We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with (DLBCL[MALT]) and without ('pure' DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of CagA and CagA-signaling molecules (p-SHP2 and p-ERK) is associated with the HP-dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored...
November 18, 2016: Blood
https://www.readbyqxmd.com/read/27856613/dorsal-horn-interneuron-derived-netrin-4-contributes-to-spinal-sensitization-in-chronic-pain-via-unc5b
#5
Yasufumi Hayano, Keiko Takasu, Yoshihisa Koyama, Moe Yamada, Koichi Ogawa, Kazuhisa Minami, Toshiyuki Asaki, Kazuhiro Kitada, Satoshi Kuwabara, Toshihide Yamashita
Because of the incomplete understanding of the molecular mechanisms that underlie chronic pain, the currently available treatments for this type of pain remain inefficient. In this study, we show that Netrin-4, a member of the axon guidance molecule family, was expressed in dorsal horn inner lamina II excitatory interneurons in the rat spinal cord. A similar expression pattern for Netrin-4 was also observed in human spinal cord. Behavioral analysis revealed that tactile and heat hyperalgesia after peripheral nerve injury or inflammation were abolished in Netrin-4-mutant rats...
November 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27851976/shp1-regulates-bone-mass-by-directing-mesenchymal-stem-cell-differentiation
#6
Menghui Jiang, Chunxing Zheng, Peishun Shou, Na Li, Gang Cao, Qing Chen, Chunliang Xu, Liming Du, Qian Yang, Jianchang Cao, Yanyan Han, Fengying Li, Wei Cao, Feng Liu, Arnold B Rabson, Arthur I Roberts, Weifen Xie, Ying Wang, Yufang Shi
No abstract text is available yet for this article.
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27831560/manipulating-the-air-filled-zebrafish-swim-bladder-as-a-neutrophilic-inflammation-model-for-acute-lung-injury
#7
Yuefei Zhang, Hongcui Liu, Junlin Yao, Yanfeng Huang, Shenlu Qin, Zheng Sun, Yingchun Xu, Shu Wan, Hongqiang Cheng, Chunqi Li, Xue Zhang, Yuehai Ke
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening diseases that are associated with high mortality rates due to treatment limitations. Neutrophils play key roles in the pathogenesis of ALI/ARDS by promoting the inflammation and injury of the alveolar microenvironment. To date, in vivo functional approaches have been limited by the inaccessibility to the alveolar sacs, which are located at the anatomical terminal of the respiratory duct in mammals...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27822318/discovery-and-replication-of-a-peripheral-tissue-dna-methylation-biosignature-to-augment-a-suicide-prediction-model
#8
Makena L Clive, Marco P Boks, Christiaan H Vinkers, Lauren M Osborne, Jennifer L Payne, Kerry J Ressler, Alicia K Smith, Holly C Wilcox, Zachary Kaminsky
BACKGROUND: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development of a biomarker can potentially improve prediction of suicidal behaviors. Prediction of our previously reported SKA2 biomarker for suicide and PTSD is substantially improved by questionnaires assessing perceived stress or anxiety and is therefore reliant on psychological assessment...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27803106/egfl6-regulates-the-asymmetric-division-maintenance-and-metastasis-of-aldh-ovarian-cancer-cells
#9
Shoumei Bai, Patrick Ingram, Yu-Chih Chen, Ning Deng, Alex Pearson, Yashar Niknafs, Patrick O'Hayer, Yun Wang, Zhong-Yin Zhang, Elisa Boscolo, Joyce Bischoff, Euisik Yoon, Ronald J Buckanovich
Little is known about the factors that regulate the asymmetric division of cancer stem-like cells (CSC). Here, we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH(+) ovarian CSC. EGFL6 signaled at least in part via the oncoprotein SHP2 with concomitant activation of ERK. EGFL6 signaling promoted the migration and asymmetric division of ALDH(+) ovarian CSC. As such, EGFL6 increased not only tumor growth but also metastasis. Silencing of EGFL6 or SHP2 limited numbers of ALDH(+) cells and reduced tumor growth, supporting a critical role for EGFL6/SHP2 in ALDH(+) cell maintenance...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27799550/targeting-of-ras-mediated-fgf-signaling-suppresses-pten-deficient-skin-tumor
#10
Grinu Mathew, Abdul Hannan, Kristina Hertzler-Schaefer, Fen Wang, Gen-Sheng Feng, Jian Zhong, Jean J Zhao, Julian Downward, Xin Zhang
Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified an autocrine FGF signaling induced by loss of Pten in keratinocytes. In this study, we demonstrate that skin hyperplasia requires FGF receptor adaptor protein Frs2α and tyrosine phosphatase Shp2, two upstream regulators of Ras signaling. Although the PI3-kinase regulatory subunits p85α and p85β are dispensable, the PI3-kinase catalytic subunit p110α requires interaction with Ras to promote hyperplasia in Pten-deficient skin, thus demonstrating an important cross-talk between Ras and PI3K pathways...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27796759/increased-src-family-kinase-activity-disrupts-excitatory-synaptic-transmission-and-impairs-remote-fear-memory-in-forebrain-shp2-deficient-mice
#11
Xunyi Yan, Bin Zhang, Wen Lu, Lin Peng, Qian Yang, Wei Cao, Shen Lin, Wenyue Yu, Xiaoming Li, Yuehai Ke, Shengtian Li, Wei Yang, Jianhong Luo
Src homolog domain-containing phosphatase 2 (Shp2) signals a variety of cellular and physiological functions including learning and memory. Dysregulation of ERK signaling is known to be responsible for the cognitive deficits associated with gain-of-function mutated Shp2 mimicking Noonan syndrome. However, here, we report that CaMKIIα-cre induced knockout (CaSKO) of Shp2 in hippocampal pyramidal neurons resulted in increased Src activity, upregulated phosphorylation of N-methyl-D-aspartate receptors (NMDARs) at Y1325 of GluN2A and at Y1472 of GluN2B, disrupted the balance of synaptic transmission, and impaired long-term potentiation and remote contextual fear memory...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27793798/epithelial-disruption-of-gab1-perturbs-surfactant-homeostasis-and-predisposes-mice-to-lung-injuries
#12
Kai Wang, Shenlu Qin, Zuyu Liang, Yun Zhang, Yingchun Xu, An Chen, Xiaohong Guo, Hongqiang Cheng, Xue Zhang, Yuehai Ke
GRB2-associated-binding protein 1 (Gab1) belongs to Gab adaptor family (Gabs), which integrates multiple signals in response to the epithelial growth factors. Recent genetic studies identified genetic variants of human Gab1 gene as potential risk factors of asthmatic inflammation. However, Gab1 functions in lungs remain largely unknown. Alveolar type-II cells (AT-IIs) are responsible for surfactant homeostasis, and essentially regulate lung inflammation following various injuries. Here, in vitro knockdown of Gab1 was shown to cause a decrease in surfactant proteins (SPs) in AT-IIs...
October 28, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27790059/comparative-analysis-of-protein-tyrosine-phosphatases-regulating-microglial-activation
#13
Gyun Jee Song, Jaehong Kim, Jong-Heon Kim, Seungeun Song, Hana Park, Zhong-Yin Zhang, Kyoungho Suk
Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS)...
October 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27783593/leukaemogenic-effects-of-ptpn11-activating-mutations-in-the-stem-cell-microenvironment
#14
Lei Dong, Wen-Mei Yu, Hong Zheng, Mignon L Loh, Silvia T Bunting, Melinda Pauly, Gang Huang, Muxiang Zhou, Hal E Broxmeyer, David T Scadden, Cheng-Kui Qu
Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity...
October 26, 2016: Nature
https://www.readbyqxmd.com/read/27776173/the-mads-box-genes-abs-shp1-and-shp2-are-essential-for-the-coordination-of-cell-divisions-in-ovule-and-seed-coat-development-and-for-endosperm-formation-in-arabidopsis-thaliana
#15
Katrin Ehlers, Amey S Bhide, Dawit G Tekleyohans, Benjamin Wittkop, Rod J Snowdon, Annette Becker
Seed formation is a pivotal process in plant reproduction and dispersal. It begins with megagametophyte development in the ovule, followed by fertilization and subsequently coordinated development of embryo, endosperm, and maternal seed coat. Two closely related MADS-box genes, SHATTERPROOF 1 and 2 (SHP1 and SHP2) are involved in specifying ovule integument identity in Arabidopsis thaliana. The MADS box gene ARABIDOPSIS BSISTER (ABS or TT16) is required, together with SEEDSTICK (STK) for the formation of endothelium, part of the seed coat and innermost tissue layer formed by the maternal plant...
2016: PloS One
https://www.readbyqxmd.com/read/27769062/bcr-abl-regulates-stat5-through-shp2-the-interferon-consensus-sequence-binding-protein-icsbp-irf8-growth-arrest-specific-2-gas2-and-calpain
#16
Elizabeth E Hjort, Weiqi Huang, Liping Hu, Elizabeth A Eklund
Icsbp/Irf8 is an interferon regulatory transcription factor that functions as a suppressor of myeloid leukemias. Consistent with this activity, Icsbp represses a set of genes encoding proteins that promote cell proliferation/survival. One such gene encodes Gas2, a calpain inhibitor. We previously found that increased Gas2-expression in Bcr-abl+ cells stabilized βcatenin; a Calpain substrate. This was of interest, because βcatenin contributes to disease progression in chronic myeloid leukemia (CML). Calpain has additional substrates implicated in leukemogenesis, including Stat5...
October 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27761214/antidepressant-activity-of-enicostemma-littorale-blume-in-shp2-protein-tyrosine-phosphatase-inhibited-animal-model-of-depression
#17
V A Doss, Dharaniyambigai Kuberapandian
BACKGROUND: The objective of this study is to develop a new animal model based on signaling pathways to understand the pathophysiology, therapy of depression, and to investigate the antidepressant activity of Enicostemma littorale which is not yet established. METHODS: Animal models of depression were raised by physical methods and administration of methyl isobutyl ketone (100 mg/kg b.w., i.p.,) and a protein tyrosine phosphatase inhibitor, sodium orthovanadate (30 mg/kg b...
2016: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/27743390/novel-g6b-gene-variant-cause-familial-autosomal-recessive-thrombocytopenia-and-anemia
#18
Motasem Melhem, Mohamed Abu-Farha, Dinu Antony, Ashraf Al Madhoun, Chiara Bacchelli, Fadi Alkayal, Irina AlKhairi, Sumi John, Mohamad Alomari, Phillip L Beales, Osama Alsmadi
OBJECTIVE: To characterize the underlying genetic and molecular defects in a consanguineous family with life-long blood disorder manifested with thrombocytopenia (low platelets count) and anemia. METHODS: Genetic linkage analysis, exome sequencing and functional genomics were carried out to identify and characterize the defective gene. RESULTS: We identification of a novel truncation mutation (p.C108*) in Chromosome 6 Open Reading Frame 25 (C6orf25) gene in this family...
October 15, 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27742545/leishmania-uses-mincle-to-target-an-inhibitory-itam-signaling-pathway-in-dendritic-cells-that-dampens-adaptive-immunity-to-infection
#19
Salvador Iborra, María Martínez-López, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M Izquierdo, Clare L Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J Robinson, Manuel Soto, Clifford A Lowell, David Sancho
C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs)...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27736153/sh2-domain-containing-phosphatase-shp-2-is-a-novel-anti-fibrotic-regulator-in-pulmonary-fibrosis
#20
Argyrios Tzouvelekis, Guoying Yu, Christian Lacks Lino Cardenas, Jose D Herazo-Maya, Rong Wang, Tony Woolard, Yi Zhang, Koji Sakamoto, Hojin Lee, Jae-Sung Yi, Giuseppe DeIuliis, Nikolaos Xylourgidis, Farida Ahangari, Patty J Lee, Vassilis Aidinis, Erica L Herzog, Robert Homer, Anton M Bennett, Naftali Kaminski
RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is a chronic fatal lung disease with dismal prognosis and no cure. The potential role of the ubiquitously expressed SH2 domain-containing-tyrosine phosphatase (SHP2) as a therapeutic target has not been studied in IPF Objectives: To determine the expression, mechanistic role and potential therapeutic utility of SHP2 in Pulmonary Fibrosis Methods: The effects of SHP2 overexpression and inhibition on fibroblast response to pro-fibrotic stimuli were analyzed in-vitro in primary human and mouse lung fibroblasts...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
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