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Jianqing Lin, Zhiyao Chen, Zhijun Huang, Feng Chen, Zeyi Ye, Shaoze Lin, Weidong Wang
As a unique member of the cadherin superfamily, T-cadherin (T-cad) has been demonstrated to be associated with gastric cancer (GC) prognosis. To elucidate the function of T-cad in GC in vitro , the present study firstly examined T-cad protein expression in normal and gastric cancer tissues and cell lines, and it was demonstrated to be significantly downregulated in gastric cancer samples compared with normal samples. Control and T-cad expression vectors were then transfected into the MGC8-03 and AGS GC cell lines...
November 2017: Experimental and Therapeutic Medicine
Shiro Fukuda, Shunbun Kita, Yoshinari Obata, Yuya Fujishima, Hirofumi Nagao, Shigeki Masuda, Yoshimitsu Tanaka, Hitoshi Nishizawa, Tohru Funahashi, Junichi Takagi, Norikazu Maeda, Iichiro Shimomura
Adiponectin, an adipocyte-derived circulating protein, accumulates in the heart, vascular endothelium, and skeletal muscles through an interaction with T-cadherin (T-cad), a unique glycosylphosphatidylinositol-anchored cadherin. Recent studies have suggested that this interaction is essential for adiponectin-mediated cardiovascular protection. However, the precise protein-protein interaction between adiponectin and T-cad remains poorly characterized. Using ELISA-based and surface plasmon analyses, we report here that T-cad fused with IgG Fc as a fusion tag by replacing its glycosylphosphatidylinositol-anchor specifically bound both hexameric and larger multimeric adiponectin with a dissociation constant of ∼1...
May 12, 2017: Journal of Biological Chemistry
Han Wang, Ling Tao, Anastasia Ambrosio, Wenjun Yan, Ross Summer, Wayne Bond Lau, Yajing Wang, Xinliang Ma
BACKGROUND: Endothelial dysfunction plays a critical role in the development of type 2 diabetes (T2DM). T-cadherin (T-cad) has gained recognition as a regulator of endothelial cell (EC) function. The present study examined whether T-cad deficiency increases vascular vulnerability in T2DM. METHODS: Vascular segments were isolated from WT or T-cad knockout mice. Endothelial function, total NO accumulation, and the expression of T-cad related proteins were determined...
January 19, 2017: Cardiovascular Diabetology
Ghorban Mohammadzadeh, Mohammad-Ali Ghaffari, Mohammad Bazyar, Alireza Kheirollah
BACKGROUND: Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes. MATERIALS AND METHODS: We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases...
2016: Advanced Biomedical Research
Andreas W Schoenenberger, Dennis Pfaff, Boris Dasen, Agne Frismantiene, Paul Erne, Therese J Resink, Maria Philippova
Close relationships exist between presence of adiponectin (APN) within vascular tissue and expression of T-cadherin (T-cad) on vascular cells. APN and T-cad are also present in the circulation but here their relationships are unknown. This study investigates associations between circulating levels of high molecular weight APN (HMW-APN) and T-cad in a population comprising 66 women and 181 men with angiographically proven stable coronary artery disease (CAD). Plasma HMW-APN and T-cad were measured by ELISA and analysed for associations with baseline clinical characteristics and with each other...
2015: PloS One
Yuki Hayano, Hong Zhao, Hiroaki Kobayashi, Kosei Takeuchi, Shigemi Norioka, Nobuhiko Yamamoto
Cortical efferent and afferent fibers are arranged in a stereotyped pattern in the intermediate zone (IZ). Here, we studied the mechanism of axonal pathway formation by identifying a molecule that is expressed in a subset of cortical axons in the rat. We found that T-cadherin (T-cad), a member of the cadherin family, is expressed in deep-layer cell axons projecting to subcortical structures, but not in upper layer callosal axons projecting to the contralateral cortex. Ectopic expression of T-cad in upper layer cells induced axons to project toward subcortical structures via the upper part of the IZ...
December 2014: Development
Agne Frismantiene, Dennis Pfaff, Audrey Frachet, Matteo Coen, Manjunath B Joshi, Kseniya Maslova, Marie-Luce Bochaton-Piallat, Paul Erne, Therese J Resink, Maria Philippova
Expression of GPI-anchored T-cadherin (T-cad) on vascular smooth muscle cells (VSMC) is elevated in vascular disorders such as atherosclerosis and restenosis which are associated with insulin resistance. Functions for T-cad and signal transduction pathway utilization by T-cad in VSMC are unknown. The present study examines the consequences of altered T-cad expression on VSMC for constitutive and insulin-induced Akt/mTOR axis signaling and contractile competence. Using viral vectors rat (WKY and SHR) and human aortic VSMCs were variously transduced with respect to T-cad-overexpression (Tcad+-VSMC) or T-cad-deficiency (shT-VSMC) and compared with their respective control transductants (E-VSMC or shC-VSMC)...
September 2014: Cellular Signalling
David I Kasahara, Alison S Williams, Leandro A Benedito, Barbara Ranscht, Lester Kobzik, Christopher Hug, Stephanie A Shore
Adiponectin, an adipose derived hormone with pleiotropic functions, binds to several proteins, including T-cadherin. We have previously reported that adiponectin deficient (Adipo(-/-)) mice have increased IL-17A-dependent neutrophil accumulation in their lungs after subacute exposure to ozone (0.3 ppm for 72 hrs). The purpose of this study was to determine whether this anti-inflammatory effect of adiponectin required adiponectin binding to T-cadherin. Wildtype, Adipo(-/-) , T-cadherin deficient (T-cad(-/-) ), and bideficient (Adipo(-/-)/T-cad(-/-) ) mice were exposed to subacute ozone or air...
2013: PloS One
Emmanouil Kyriakakis, Kseniya Maslova, Audrey Frachet, Nicola Ferri, Alessandro Contini, Dennis Pfaff, Paul Erne, Therese J Resink, Maria Philippova
Reciprocal cross-talk between receptor tyrosine kinases (RTKs) and classical cadherins (e.g. EGFR/E-cadherin, VEGFR/VE-cadherin) has gained appreciation as a combinatorial molecular mechanism enabling diversification of the signalling environment and according differential cellular responses. Atypical glycosylphosphatidylinositol (GPI)-anchored T-cadherin (T-cad) was recently demonstrated to function as a negative auxiliary regulator of EGFR pathway activation in A431 squamous cell carcinoma (SCC) cells. Here we investigate the reciprocal impact of EGFR activation on T-cad...
May 2013: Cellular Signalling
Alison S Williams, David I Kasahara, Norah G Verbout, Alexey V Fedulov, Ming Zhu, Huiqing Si, Allison P Wurmbrand, Christopher Hug, Barbara Ranscht, Stephanie A Shore
Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13) is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT), T-cadherin deficient (T-cad(-/-)) and adiponectin and T-cad bideficient mice to ovalbumin (OVA) and challenged the mice with aerosolized OVA or PBS...
2012: PloS One
Min Wang, Ying-Ru Chai, Chuan-Shi Xiao, Xu-Jing Zhao, Na Wei, Rui Bai, Yun-Fei Bian
The aim of the present study was to investigate the effects of adiponectin (APN) on the expression of T-cadherin in cultured Sprague-Dawley (SD) rat cardiomyocytes injured by hypoxia/reoxygenation (H/R). Primary myocardial cells from neonatal rats were obtained by enzymatic digestion. The cells were divided into control group, H/R group and H/R+APN (3, 10, 20 and 30 μg/mL) groups. The H/R group was incubated in anoxic environment (anoxic solution saturated with high concentration N2) for 3 h, and then in the reoxygenation environment (the reoxygenation solution saturated with pure oxygen) for 1 h...
June 25, 2012: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Emmanouil Kyriakakis, Kseniya Maslova, Maria Philippova, Dennis Pfaff, Manjunath B Joshi, Stanislaw A Buechner, Paul Erne, Thérèse J Resink
Genetic and epigenetic studies in different cancers, including cutaneous carcinomas, have implicated T-cadherin (T-cad) as a tumor suppressor. Immunohistochemical and in vitro studies have suggested that T-cad loss promotes incipient invasiveness in cutaneous squamous cell carcinoma (SCC). Molecular mechanisms are unknown. This study found that the main consequence of T-cad silencing in SCC is facilitation of ligand-dependent EGFR activation, whereas T-cad overexpression impedes EGFR activation. Gain- and loss-of-function studies in A431 SCC cells demonstrate T-cad-controlled responsiveness to EGF with respect to pharmacological inhibition of EGFR and to diverse signaling and functional events of the EGFR activation cascade (EGFR phosphorylation, internalization, nuclear translocation, cell retraction/de-adhesion, motility, invasion, integrin β1, and Rho small GTPases such as RhoA, Rac1, and Cdc42 activation)...
September 2012: Journal of Investigative Dermatology
Maria Philippova, Manjunath B Joshi, Dennis Pfaff, Emmanouil Kyriakakis, Kseniya Maslova, Paul Erne, Thérèse J Resink
AIMS: T-cadherin (T-cad) is a glycosylphosphatidylinositol-anchored cadherin family member. Experimental, clinical, and genomic studies suggest a role for T-cad in vascular disorders such as atherosclerosis and hypertension, which are associated with endothelial dysfunction and insulin resistance (InsRes). In endothelial cells (EC), T-cad and insulin activate similar signalling pathways [e.g. PI3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)] and processes (e.g. angiogenesis)...
March 1, 2012: Cardiovascular Research
Björn Tyrberg, Philip Miles, Krist T Azizian, Martin S Denzel, Maria L Nieves, Edward Z Monosov, Fred Levine, Barbara Ranscht
Glucose homeostasis depends on adequate control of insulin secretion. We report the association of the cell-adhesion and adiponectin (APN)-binding glycoprotein T-cadherin (Cdh13) with insulin granules in mouse and human β-cells. Immunohistochemistry and electron microscopy of islets in situ and targeting of RFP-tagged T-cadherin to GFP-labeled insulin granules in isolated β-cells demonstrate this unusual location. Analyses of T-cadherin-deficient (Tcad-KO) mice show normal islet architecture and insulin content...
November 2011: Islets
Dennis Pfaff, Maria Philippova, Emmanouil Kyriakakis, Kseniya Maslova, Katharina Rupp, Stanislaw A Buechner, Giandomenica Iezzi, Giulio C Spagnoli, Paul Erne, Therese J Resink
Mechanisms underlying cutaneous squamous cell carcinoma (SCC) tumour growth and invasion are incompletely understood. Our previous pathological and in vitro studies suggest that cell surface glycoprotein T-cadherin (T-cad) might be a controlling determinant of the behaviour of SCC. Here we used a murine xenograft model to determine whether T-cad modulates SCC tumour progression in vivo. Silencing or up-regulation of T-cad in A431 (shTcad or Tcad(+) , respectively) both resulted in increased tumour expansion in vivo...
December 2011: Journal of Pathology
YingLi Lin, Guang Sun, XiaoQiang Liu, YeGang Chen, ChunTing Zhang
OBJECTIVE: To investigate the clinical significance of T-cadherin (T-cad) tissue expression in patients with bladder transitional cell carcinoma (TCC). MATERIALS AND METHODS: T-cad expression in 113 bladder TCC specimens and 37 normal controls were examined by immunohistochemical staining, and the results were correlated with clinicopathologic parameters. The χ(2) test, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used for statistical analysis...
2011: Urologia Internationalis
Maria Philippova, Yves Suter, Stefan Toggweiler, Andreas W Schoenenberger, Manjunath B Joshi, Emmanouil Kyriakakis, Paul Erne, Thérèse J Resink
AIMS: The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. METHODS AND RESULTS: Immunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs...
March 2011: European Heart Journal
Emmanouil Kyriakakis, Maria Philippova, Manjunath B Joshi, Dennis Pfaff, Valery Bochkov, Taras Afonyushkin, Paul Erne, Therese J Resink
Endoplasmic reticulum (ER) stress activated by perturbations in ER homeostasis induces the unfolded protein response (UPR) with chaperon Grp78 as the key activator of UPR signalling. The aim of UPR is to restore normal ER function; however prolonged or severe ER stress triggers apoptosis of damaged cells to ensure protection of the whole organism. Recent findings support an association of ER stress-induced apoptosis of vascular cells with cardiovascular pathologies. T-cadherin (T-cad), an atypical glycosylphosphatidylinositol-anchored member of the cadherin superfamily is upregulated in atherosclerotic lesions...
September 2010: Cellular Signalling
Sophie Collot-Teixeira, John L McGregor, Kira Morser, Lara Chalabreysse, Chris McDermott-Roe, Catherine Cerutti, Adriana Guzman, Jean-Baptiste Michel, Pascale Boissonnat, Laurent Sebbag, Françoise Thivolet-Bejui, Gianpiero Bricca, Jean-François Obadia, Ana Roussoulières
BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR). METHODS: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas...
July 2010: Journal of Heart and Lung Transplantation
D Pfaff, M Philippova, S A Buechner, K Maslova, T Mathys, P Erne, T J Resink
BACKGROUND: Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol-anchored T-cadherin (T-cad) is highly expressed in the basal keratinocyte layer of skin. The role of T-cad in keratinocyte biology and pathology is unclear. OBJECTIVES: To define the role of T-cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain-of-function and loss-of-function studies in vitro and through examination of T-cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation...
August 2010: British Journal of Dermatology
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