Human giant larvae-1 promotes migration and invasion of malignant glioma cells by regulating N-cadherin

Human giant larvae-1 (Hugl-1) is a human homologue of Drosophila tumor suppressor lethal (2)-giant larvae and has been reported to be involved in the development of human malignancies. Previous studies performed by our group demonstrated that Hugl-1 inhibits glioma cell proliferation in an intracranial model of nude mice. However, the exact molecular mechanisms underlying the participation of Hugl-1 in glioma invasion and migration, and in the depolarizing process remain largely unknown. Utilizing the U251-MG cells with stable expression of Hugl-1, the present study used wound healing, Transwell invasion and western blot assays to explore the role and specific mechanism of Hugl-1 in glioma invasion and migration. The results of the present study demonstrated that overexpression of Hugl-1 decreased cell-cell adhesion and increased cell-cell extracellular matrix adhesion. In addition, overexpression of Hugl-1 promoted pseudopodia formation, glioma cell migration and invasion. The molecular mechanism of action involved the negative regulation of N-cadherin protein levels by Hugl-1. Overexpression or knockdown of N-cadherin partially suppressed or enhanced the effects of Hugl-1 on glioma cell migration and invasion, respectively. Furthermore, Hugl-1 inhibited cell proliferation, while promoting cell migration, which suggests that it may serve a two-sided biological role in cellular processes. Taken together, these results suggest that Hugl-1 promotes the migration and invasion of malignant glioma cells by decreasing N-cadherin expression. Thus, Hugl-1 may be applied in the development of targeted and personalized treatment.     

Expression of podoplanin and classical cadherins in salivary gland epithelial cells of klotho-deficient mice

We have recently shown that salivary gland myoepithelial cells express podoplanin. Podoplanin indirectly binds the actin filament network which links classical cadherins. The study here is aimed to investigate the expression of podoplanin and cadherins on salivary gland myoepithelial cells and the changes in the aging cells using klotho-deficient (kl/kl) mice. The submandibular glands of kl/kl mouse lack granular ducts which express klotho in wild type mice, suggesting that klotho may be a gene responsible for granular duct development. Although aging resulted in growth suppression of myoepithelial cells because of the sparse distribution of the cells in kl/kl mouse salivary glands, the expression of podoplanin and E-cadherin was shown in aging myoepithelial cells. It is thought that podoplanin participates in the actin-E-cadherin networks which are maintained in aging myoepithelial cells. It was also shown that granular ducts were filled with P-cadherin, and that the P-cadherin amount was larger in the wild type mouse submandibular glands than in the sublingual and parotid glands of wild type mouse, and in the submandibular glands of kl/kl mouse. These findings suggest that the granular duct is an organ secreting soluble P-cadherin into the saliva.     

N-cadherin 在胆管癌组织中的表达及意义

目的 探讨N-cadherin 在胆管癌组织中的表达情况及临床病理意义。方法 应用免疫组织化学方法检测N-cadherin在胆管癌及胆管良性病变组织中的表达,并对N-cadherin的表达与临床病理特征的关系进行分析。结果 31例胆管癌组织中N-cadherin表达的阳性率为58.1％(18／31),15例胆管炎组织无一例阳性表达(O％),差异有统计学意义(X2=14.309,P0.05)。结论 N-cadherin在胆管癌组织中的表达升高,并与其神经浸润转移相关。     

靶向沉默ADAM10基因对心肌细胞N-cadherin加工的影响

目的:研究心肌细胞中解整合素金属蛋白酶家族(ADAMs)成员ADAM10在神经型钙黏蛋白(N-cadherin)底物加工过程中的重要性,为探求该加工途径在维持心肌组织结构形态和完整性中的作用打下基础。方法:将质粒sc-270165 ADAM10 siRNA(r)转染入大鼠心肌细胞(H9c2),建立ADAM10稳定沉默的心肌细胞株。通过Western blotting检测心肌细胞N-cadherin及其C末端片段(CTF)的蛋白表达,流式细胞术检测心肌细胞表面N-cadherin的表达。利用黏附实验检测其对细胞黏附能力的影响。结果:与阴性对照组相比,ADAM10基因沉默组心肌细胞N-cadherin蛋白表达提高,CTF蛋白表达减少;细胞表面N-cadherin的表达增多,心肌细胞黏附能力提高。结论:心肌细胞中ADAM10在N-cadherin的加工水解过程中可能发挥了作用。     

Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

Peripheral interactions between nociceptive fibers and mast cells contribute to inflammatory pain, but little is known about mechanisms mediating neuro-immune communication. Here we show that metalloproteinase MT5-MMP (MMP-24) is an essential mediator of peripheral thermal nociception and inflammatory hyperalgesia. We report that MT5-MMP is expressed by CGRP-containing peptidergic nociceptors in dorsal root ganglia and that Mmp24-deficient mice display enhanced sensitivity to noxious thermal stimuli under basal conditions. Consistently, mutant peptidergic sensory neurons hyperinnervate the skin, a phenotype that correlates with changes in the regulated cleavage of the cell-cell adhesion molecule N-cadherin. In contrast to basal nociception, Mmp24^−/− mice do not develop thermal hyperalgesia during inflammation, a phenotype that appears associated with alterations in N-cadherin-mediated cell-cell interactions between mast cells and sensory fibers. Collectively, our findings demonstrate an essential role of MT5-MMP in the development of dermal neuro-immune synapses and suggest that this metalloproteinase may be a target for pain control.     

The inverted neurogenetic gradient of the mammalian isocortex: development and evolution

In this paper we review recent evidence on the molecular control of cell migration in the isocortex, and present an hypothesis for the evolutionary origin of the inside-out neurogenetic gradient of this structure. We suggest that there are at least two key factors involved in the acquisition of the inside-out gradient: (i) the expression of the protein reelin, which arrests the migration of cortical plate cells by detaching them from the radial glial fiber. This permits younger neurons to use the same fiber to migrate past the previous neurons; and (ii) the second factor is an intracellular signaling pathway dependent on a cyclin-dependent protein kinase (Cdk5). Cdk5 may work by inhibiting N-cadherin mediated cell aggregation as young cells cross the cortical plate, permitting them to move to the more superficial layers. Interestingly, the mutation in Cdk5 affects the migration of only those cells belonging to superficial layers, which are considered to be an evolutionary acquisition of the mammalian isocortex.     

N-cadherin、E-cadherin在直肠癌中的表达及临床意义

目的探讨N-cadherin,E-cadherin(N-钙粘附素、E-钙粘附素)在直肠癌中的表达与临床病理因素的关系。方法采用免疫组织化学染色法检测86例直肠癌及正常直肠组织标本N-cadherin,E-cadherin的表达。结果N-cadherin,E-cadherin表达阳性均为39例(45%),阴性均为47例(55%),N-cadherin阳性表达率与E-cadherin阴性表达率与肿瘤恶性程度、分期、侵袭、转移及预后呈正相关,对比组之间的差异具有非常显著性(P<0.01);86例正常直肠组织细胞不表达N-cadherin,而E-cadherin呈高表达。结论N-cadherin反常表达和E-cadherin低表达或不表达是直肠癌浸润及转移的重要因素,直接影响5年生存率,N-cadherin,E-cadherin可作为判定直肠癌恶性程度及预后的重要指标。     

N-Cadherin,E-Cadherin在直肠癌中的表达及临床意义

目的探讨N-,E-Cadherin(N-钙粘附素、E-钙粘附素)在直肠癌中的表达与临床病理因素的关系.方法采用免疫组织化学染色法检测86例直肠癌及正常直肠组织标本N-E-Cadherin的表达.结果N-,E-Cadherin表达阳性均为39例(45%),阴性均为47例(55%),N-Cadherin阳性表达率与E-Cadherin阴性表达率与肿瘤恶性程度、分期、侵袭、转移及预后呈正相关,对比组之间的差异具有非常显著性(P＜0.01);86例正常直肠组织细胞不表达N-Cadherin,而E-Cadherin呈高表达.结论N-Cadherin反常表达和E-Cadherin低表达或不表达是直肠癌浸润及转移的重要因素,直接影响五年生存率,N-,E-Cadherin可作为判定直肠癌恶性程度及预后的重要指标.     

E-cadherin maintains the activity of neural stem cells and inhibits the migration

Cadherins are important adhesion molecules that mediate adhesions and communications between cells. These molecules participate in the formation and maintenance of multicellular organisms including the stem cells. E-cadherin is one of the classic cadherins which is reported to be essential for the survival and self-renewal of embryonic stem cells. Moreover, it could induce cell proliferation inhibitory signaling to regulate cell proliferation. In our study, we over-expressed and silenced E-cadherin in NSCs by lentiviral ways. Transgenic cells were confirmed by both quantitative RT-PCR and western blot. Results of MTT assay showed that over-expression of E-cadherin could enhance the cell activity. Furthermore, we performed Transwell chamber assay to analyze its role in regulation of cell migration. The results showed that the migration percent of over-expression cells was lower than control. Our results indicated that E-caherin would maintain the stemness of NSCs and reduce cells migration.