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https://www.readbyqxmd.com/read/28814887/shp2-overexpression-enhances-the-invasion-and-metastasis-of-ovarian-cancer-in-vitro-and-in-vivo
#1
ZhongQian Hu, Jia Li, Qi Gao, Shuping Wei, Bin Yang
PURPOSE: SHP2 has roles in a variety of signal transduction pathways and in many important cellular processes, including proliferation, differentiation, movement regulation, and apoptosis. In addition, SHP2 expression is closely associated with multiple types of malignancies. In this study, we examined the role of SHP2 in epithelial ovarian cancer. PATIENTS AND METHODS: SHP2 expression in cancer and normal ovarian tissue specimens was evaluated by immunohistochemical staining and Western blot analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28814789/differential-oxidation-of-protein-tyrosine-phosphatases-during-zebrafish-caudal-fin-regeneration
#2
Wei Wu, Alexander James Hale, Simone Lemeer, Jeroen den Hertog
Zebrafish have the capacity to regenerate lost tissues and organs. Amputation of the caudal fin results in a rapid, transient increase in H2O2 levels emanating from the wound margin, which is essential for regeneration, because quenching of reactive oxygen species blocks regeneration. Protein-tyrosine phosphatases (PTPs) have a central role in cell signalling and are susceptible to oxidation, which results in transient inactivation of their catalytic activity. We hypothesized that PTPs may become oxidized in response to amputation of the caudal fin...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814604/macrophage-restricted-shp2-tyrosine-phosphatase-acts-as-a-rheostat-for-mmp12-through-tgf-%C3%AE-activation-in-the-prevention-of-age-related-emphysema-in-mice
#3
Jiaqi Xu, Bo Tao, Xiaohong Guo, Shiyi Zhou, Yongda Li, Yuqin Zhang, Zanhua Zhou, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Persistent activation of macrophages in lungs plays a critical role in the production of matrix metalloproteinases (MMPs) that contributes to the destruction of alveolar walls, a hallmark for pulmonary emphysema. Dysregulated TGF-β1 signaling has been an essential determinant in the elevation of MMPs during the development of emphysema. Nevertheless, the mechanism for this MMP-dependent pathogenesis has yet to be clearly investigated. Recently, we identified an important role for tyrosine phosphatase Src homology domain-containing protein tyrosine phosphatase 2 (Shp2) in regulating the activation of alveolar macrophages...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28768764/src-homology-2-domain-containing-phosphotyrosine-phosphatase-2-shp2-controls-surface-glua1-in-synaptic-homeostasis
#4
Bin Zhang, Wen Lu
Src Homology 2 Domain Containing Phosphotyrosine Phosphatase 2 (Shp2) functions in synaptic plasticity, learning, and memory. However, the precise mechanisms by which this multifunctional protein contributes to synaptic function remains largely unknown. Homeostatic plasticity may be viewed as a process of bi-directional synaptic scaling, up or down. Through this process neuronal circuitry stability is maintained so that changes in synaptic strength may be preserved under changing conditions. Better understanding of these processes is needed...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28761355/ergosterol-peroxide-inhibits-ovarian-cancer-cell-growth-through-multiple-pathways
#5
Weiwei Tan, Meihong Pan, Hui Liu, Hequn Tian, Qing Ye, Hongda Liu
Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28754897/reciprocal-regulation-of-tlr2-mediated-ifn-%C3%AE-production-by-shp2-and-gsk3%C3%AE
#6
Jin Hee Park, Ryeojin Ko, Soo Young Lee
Toll-like receptor 2 (TLR2) mediates the innate immune response to bacterial lipopeptides and peptidoglycans by stimulating the production of inflammatory cytokines. However, the mechanisms by which TLR2 signaling regulates type I interferon (IFN)-β production are poorly understood. Here, we identified Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) as a negative regulator of TLR2-induced IFN-β production. Pharmacological inhibition or reduced expression of SHP2 potentiated TLR2 agonist-mediated IFN-β transcription and STAT1 activation, whereas overexpression of SHP2 impaired IFN-β transcription and STAT1 activation...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743735/lilrb4-deficiency-aggravates-the-development-of-atherosclerosis-and-plaque-instability-by-increasing-the-macrophage-inflammatory-response-via-nf-%C3%AE%C2%BAb-signaling
#7
Zhou Jiang, Juan-Juan Qin, Yaxing Zhang, Wen-Lin Cheng, Yan-Xiao Ji, Fu-Han Gong, Xue-Yong Zhu, Yan Zhang, Zhi-Gang She, Zan Huang, Hongliang Li
Atherosclerosis is a chronic inflammatory disease. LILRB4 is associated with the pathological processes of various inflammatory diseases. However, the potential function and underlying mechanisms of LILRB4 in atherogenesis remain to be investigated. In this study, LILRB4 expression was examined in both human and mouse atherosclerotic plaques. The effects and possible mechanisms of LILRB4 in atherogenesis and plaque instability were evaluated in LILRB4(-/-)ApoE(-/-) and ApoE(-/-) mice fed a high-fat diet. We found that LILRB4 was located primarily in macrophages, and its expression was up-regulated in atherosclerotic lesions from human coronary arteries and mouse aortic roots...
July 25, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28742699/understanding-and-resetting-radiation-sensitivity-in-rectal-cancer
#8
Katherine A Kelley, Rebecca A Ruhl, Shushan R Rana, Elizabeth Dewey, Cristina Espinosa, Charles R Thomas, Robert G Martindale, Sudarshan Anand, Vassiliki L Tsikitis
OBJECTIVE: The aim of the study was to explore specific microRNAs (miRs) in rectal cancer that would predict response to radiation and identify target pathways that may be exploited for neoadjuvant therapies. SUMMARY BACKGROUND DATA: Chemoradiotherapy (CRT) response is a predictor of survival in rectal cancer. Studies have demonstrated changes in RNA expression correlate with chemoradiation sensitivity across cancers. METHODS: Forty-five rectal cancer patients, partial responders (PR = 18), nonresponders (NR = 13), and complete responders (CR = 14) to CRT, as defined by a tumor regression score, were examined...
July 24, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28724938/a-novel-role-for-rar%C3%AE-agonists-as-apolipoprotein-ciii-inhibitors-identified-from-high-throughput-screening
#9
Sang Jun Lee, Madhupriya Mahankali, Abdallah Bitar, Huafei Zou, Elizabeth Chao, Hung Nguyen, Jose Gonzalez, Dawna Caballero, Mitch Hull, Danling Wang, Peter G Schultz, Weijun Shen
Elevated triglyceride (TG) levels are well-correlated with the risk for cardiovascular disease (CVD). Apolipoprotein CIII (ApoC-III) is a key regulator of plasma TG levels through regulation of lipolysis and lipid synthesis. To identify novel regulators of TG levels, we carried out a high throughput screen (HTS) using an ApoC-III homogenous time resolved fluorescence (HTRF) assay. We identified several retinoic acid receptor (RAR) agonists that reduced secreted ApoC-III levels in human hepatic cell lines. The RARα specific agonist AM580 inhibited secreted ApoC-III by >80% in Hep3B cells with an EC50 ~2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694388/annexin-a2-supports-pulmonary-microvascular-integrity-by-linking-vascular-endothelial-cadherin-and-protein-tyrosine-phosphatases
#10
Min Luo, Elle C Flood, Dena Almeida, LunBiao Yan, David A Berlin, Paul M Heerdt, Katherine A Hajjar
Relative or absolute hypoxia activates signaling pathways that alter gene expression and stabilize the pulmonary microvasculature. Alveolar hypoxia occurs in disorders ranging from altitude sickness to airway obstruction, apnea, and atelectasis. Here, we report that the phospholipid-binding protein, annexin A2 (ANXA2) functions to maintain vascular integrity in the face of alveolar hypoxia. We demonstrate that microvascular endothelial cells (ECs) from Anxa2(-/-) mice display reduced barrier function and excessive Src-related tyrosine phosphorylation of the adherens junction protein vascular endothelial cadherin (VEC)...
July 10, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28690843/the-role-of-pd-1-in-regulation-of-macrophage-apoptosis-and-its-subversion-by-leishmania-donovani
#11
Shalini Roy, Purnima Gupta, Shreyasi Palit, Moumita Basu, Anindita Ukil, Pijush K Das
Programmed death-1 receptor (PD-1) expressed in many immune cells is known to trigger T-cell exhaustion but the significance of macrophage-associated PD-1 in relevance to macrophage apoptosis is not known. This study is aimed to delineate whether PD-1 pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, Leishmania donovani modulates PD-1 pathway for protecting its niche. Resting macrophages when treated with H2O2 showed increased PD-1 expression and apoptosis, which was further enhanced on PD-1 agonist treatment...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28658669/shp2-negatively-regulates-hla-abc-and-pd-l1-expression-via-stat1-phosphorylation-in-prostate-cancer-cells
#12
Zhuqing Liu, Yu Zhao, Juemin Fang, Ran Cui, Yuanyuan Xiao, Qing Xu
Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is a ubiquitous protein tyrosine phosphatase that activates the signal transduction pathways of several growth factors and cytokines. In our study, SHP2 expression was very high in prostate cancer (PCa) cell lines, and the expression of phospho-signal transducer and activator of transcription 1 (p-STAT1) and STAT1 was very low. SHP2 knockdown upregulated the expression of p-STAT1 and downregulated phospho-extracellular signal regulated kinase (p-ERK)...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643869/mechanotransduction-properties-of-the-cytoplasmic-tail-of-pecam-1
#13
Jessica L Snyder, Elena McBeath, Tamlyn N Thomas, Yi Jen Chiu, Robert L Clark, Keigi Fujiwara
BACKGROUND INFORMATION: Vascular endothelial cells (ECs) are a well-known cell system used in the study of mechanobiology. Using cultured ECs, we found that platelet EC adhesion molecule 1 (PECAM-1, CD31), a cell adhesion protein localised to regions of EC-EC contact, was rapidly tyrosine phosphorylated in ECs exposed to shear or cyclic stretch. Src-homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) binds phosphorylated PECAM-1 and activates the extracellular signal-regulated kinase1/2 (ERK1/2) signalling cascade, a known flow-activated signalling pathway...
June 23, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28633870/omega-3-free-fatty-acids-attenuate-insulin-promoted-breast-cancer-cell-proliferation
#14
Yang Guo, Sheng-Long Zhu, Yi-Kuan Wu, Zhao He, Yong-Quan Chen
High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28606940/shp1-function-in-myeloid-cells
#15
REVIEW
Clare L Abram, Clifford A Lowell
The motheaten mouse was first described in 1975 as a model of systemic inflammation and autoimmunity, as a result of immune system dysregulation. The phenotype was later ascribed to mutations in the cytoplasmic tyrosine phosphatase Shp1. This phosphatase is expressed widely throughout the hematopoietic system and has been shown to impact a multitude of cell signaling pathways. The determination of which cell types contribute to the different aspects of the phenotype caused by global Shp1 loss or mutation and which pathways within these cell types are regulated by Shp1 is important to further our understanding of immune system regulation...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28599500/notable-roles-of-ezh2-and-dnmt1-in-epigenetic-dormancy-of-the-shp1-gene-during-the-progression-of-chronic-myeloid-leukaemia
#16
Jing Wang, Luoming Hua, Ming Guo, Lin Yang, Xiaojun Liu, Yanmeng Li, Xiaoyan Shang, Jianmin Luo
Tumor development is associated with the methylation of cytosine-guanine (CpG) islands. The occurrence of methylation requires several factors, such as DNA methylation systems and polycomb group (PcG) proteins. At present, novel drugs are needed for the treatment of chronic myeloid leukaemia (CML), particularly considering the current prognosis of CML. The methylation status of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1) gene, a negative regulator of signal transduction, has been identified as being altered in numerous haematological malignancies...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28593618/rig-i-a-multifunctional-protein-beyond-a-pattern-recognition-receptor
#17
REVIEW
Xiao-Xiao Xu, Han Wan, Li Nie, Tong Shao, Li-Xin Xiang, Jian-Zhong Shao
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations...
June 8, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28582432/in-vivo-efficacy-of-the-akt-inhibitor-arq-092-in-noonan-syndrome-with-multiple-lentigines-associated-hypertrophic-cardiomyopathy
#18
Jianxun Wang, Vasanth Chandrasekhar, Giovanni Abbadessa, Yi Yu, Brian Schwartz, Maria I Kontaridis
Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age...
2017: PloS One
https://www.readbyqxmd.com/read/28551626/lipoic-acid-decreases-the-viability-of-breast-cancer-cells-and-activity-of-ptp1b-and-shp2
#19
Alicja Kuban-Jankowska, Magdalena Gorska-Ponikowska, Michal Wozniak
BACKGROUND: Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. MATERIALS AND METHODS: We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28550197/viral-rna-unprimed-rig-i-restrains-stat3-activation-in-the-modulation-of-regulatory-t-cell-th17-cell-balance
#20
Hui Yang, He-Zhou Guo, Xian-Yang Li, Jian Lin, Wu Zhang, Jun-Mei Zhao, Hong-Xin Zhang, Sai-Juan Chen, Zhu Chen, Jiang Zhu
Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4(+) T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I(-/-) CD4(+) T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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