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GLUL stabilizes n-cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with n stage and TnM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to n-cadherin, increased the stability of n-cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower n-cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of n-cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes n-cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL n-cadherin β-Catenin Enzyme

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宫颈癌组织中DEK与MMP-7、n-cadherin的表达及临床意义

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医学信息 2024年第2期37卷 95-98页

作者：曹江杨麦青葛莉乔海燕高利利张庆军潍坊市中医院妇产科潍坊市人民医院病理科潍坊市中医院脑病科

目的观察宫颈癌组织中DEK与MMP-7、n-cadherin的表达情况，并探讨其在宫颈癌的临床意义。方法收集2016年1月-2021年12月在潍坊市中医院手术切除，并经病理确诊为宫颈鳞状细胞癌组织80例，选取癌旁正常宫颈组织标本50例，采用免疫组化... 详细信息

目的观察宫颈癌组织中DEK与MMP-7、n-cadherin的表达情况，并探讨其在宫颈癌的临床意义。方法收集2016年1月-2021年12月在潍坊市中医院手术切除，并经病理确诊为宫颈鳞状细胞癌组织80例，选取癌旁正常宫颈组织标本50例，采用免疫组化法检测两组中DEK与MMP-7、n-caherin蛋白的表达情况，分析三者与宫颈癌临床病理特征的关系，并进一步分析三种蛋白在宫颈癌中表达的相关性。结果 DEK、MMP-7、n-cadherin在宫颈癌组织中的表达高于癌旁正常宫颈组织（Pn-caherin的高表达与宫颈癌分化程度、淋巴结转移及TnM分期相关（P0.05）。宫颈癌中DEK的表达分别与MMP-7(r=0.269,P=0.008)、n-caherin(r=0.295,P=0.004)的表达呈正相关。结论 DEK与宫颈癌的发生有关，且与宫颈癌的组织分化及浸润转移有关，其在宫颈癌中的作用机制可能与MMP-7、n-caherin有关。

关键词：宫颈癌 DEK MMP-7 n-cadherin

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Cortactin/n-cadherin信号轴在病理性心肌肥大中的作用

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中国药理学通报 2024年第2期40卷 234-242页

作者：王钺镁喻文静孙袭孟张静路静刘培庆中山大学药学院广东广州510006

目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,nRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6... 详细信息

目的探究皮层肌动蛋白结合蛋白(Cortactin)对异丙肾上腺素(isoprenaline,ISO)诱导的病理性心肌肥大的调控作用及其机制。方法采用ISO刺激新生大鼠心肌细胞(neonatal rat cardiomyocytes,nRCMs)24 h,在细胞水平建立心肌肥大模型;C57BL/6小鼠皮下注射ISO 1周,在动物水平建立心肌肥大模型。采用RT-qPCR检测mRnA的变化;免疫印迹法检测相应蛋白含量的变化;免疫荧光法检测Cortactin的亚细胞定位及表达量的变化;采用腺病毒感染的方法过表达Cortactin,通过转染小干扰RnA敲低Cortactin。结果在细胞和动物水平上,成功建立ISO诱导的心肌肥大模型,均观察到ISO引起Cortactin和n型钙黏连蛋白(n-cadherin)水平降低;过表达Cortactin可逆转ISO导致的n-cadherin蛋白水平的降低及心肌细胞肥大反应;敲低Cortactin则显示相反的效应。结论Cortactin可能联合n-cadherin通过增强心肌细胞之间的连接,发挥抗心肌肥大的作用。

关键词：异丙肾上腺素心肌肥大心肌细胞肌动蛋白结合蛋白 n-cadherin 细胞连接

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n-cadherin expression in the midbrain substantia nigra of perinatal rats

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neural Regeneration Research 2008年第10期3卷 1136-1140页

作者： Junping Cao Yu Sun Xia Du Dianshuai Gao Department of neurobiology Xuzhou Medical College Xuzhou 221002 Jiangsu Province China

BACKGROUnD： Cellular adhesion molecule mediates the effects of glial cell line-derived neurotrophic factor in dopaminergic neurons during nervous system development. It is assumed that cellular adhesion molecule plays an important role in dopaminergic neuron development. OBJECTIVE： To investigate n-cadherin expression in the midbrain substantia nigra during rat development. DESIGn, TIME AnD SETTInG： The developmental biology, controlled study was performed at the Laboratory of Research Center of neurobiology, Xuzhou Medical College, China from April to October 2007. MATERIALS： Sprague Dawley rats （embryonic days 16, 18, and 20, as well as postnatal days 1, 3, 7, 14, and 21） were selected for this study. n-cadherin antibody was purchased from Santa Cruz, USA. METHODS： n-cadherin expression in the midbrain substantia nigra of perinatal rats was detected using reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry methods. n-cadherin-positive cells were counted. MAIn OUTCOME MEASURES： n-cadherin mRnA, protein, and positive cells in the rat midbrain substantia nigra were quantified. RESULTS： The results of reverse transcription polymerase chain reaction and Western blot demonstrated that altered n-cadherin mRnA levels were similar to protein levels in the midbrain substantia nigra. n-cadherin mRnA and protein expression was low in the midbrain substantia nigra of embryonic day 16 rats but gradually increased, and reached a peak at postnatal day 1. n-cadherin mRnA and protein levels were still high at postnatal days 3 and 7, but significantly decreased at postnatal day 14. There was no significant difference in n-cadherin mRnA and protein expression between postnatal days 14 and 21 （P 〉 0.05）. The immunohistochemistry results demonstrated that there was no significant difference in the quantity of n-cadherin-positive cells per area in rats from embryonic day 16 to postnatal day 7 （P 〉 0.05）. The quantity of n-cadherin-positive cells per a

关键词： n-cadherin substantia nigra nervous system development

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Transformable peptide nanoparticles inhibit the migration of n-cadherin overexpressed cancer cells

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Chinese Chemical Letters 2020年第7期31卷 1787-1791页

作者： Jiaqi Fan Yu Fan Zijin Wei Yijing Li Xiangdan Li Lei Wang Hao Wang Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education&Hubei Key Laboratory of Catalysis and Materials Science South-Central University for NationalitiesWuhan 430074China GAS Center for Excellence in nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing 100190China

About 90%cancer-related mortality results from the cancer metastasis,which generally undergoes after epithelial-mesenchymal transition(EMT)process.n-cadherin,overexpressed on cancer cell surface during EMT,can enhance the migration of cancer *** rein,we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK(BFS)that can block n-cadherin for inhibiting cancer migration and *** peptide BFS consists of three modules including(1)the hydrophobic bis-pyrene(BP)unit for forming and locating nanoparticles,(2)the KLVFF peptide sequence for forming and stabilizing fibrous structures and(3)the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to *** peptide BFS can form nanoparticles in PBS,which can transform to nanofibers when targeting and binding to *** nanofibers inhibit the migration of n-cadherin overexpressed MDA-MB-436 cancer *** peptide BFS shows 83.6%inhibiting rate in cells wound healing *** addition,the inhibition rate is 67.9%when the BFS applied in transwell migration *** results indicate that the BFS has excellent ability to inhibit migration of cancer *** self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.

关键词： Self-assembly Peptide n-cadherin Cancer Ligand-receptor interaction

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Paradoxical expression pattern of the epithelial mesenchymal transition-related biomarkers CD44, SLUG, n-cadherin and VSIG1/Glycoprotein A34 in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2017年第11期9卷 436-443页

作者： Attila Kovecsi Simona Gurzu Zoltan Szentirmay Zsolt Kovacs Tivadar Jr Bara Ioan Jung Department of Pathology University of Medicine and Pharmacy Research Center University of Medicine and Pharmacy Department of Pathology National Institute of Oncology Department of Biochemistry University of Medicine and Pharmacy Department of Surgery University of Medicine and Pharmacy

AIM To evaluate the immunohistochemical(IHC) expression of five biomarkers, commonly involved in epithelial mesenchymal/mesenchymal epithelial transition(EMT/MET), in gastrointestinal stromal tumors(GISTs). METHODS In 80 consecutive GISTs the IHC examinations were performed using the EMT-related antibodies E-cadherin,n-cadherin, SLUG, V-set and immunoglobulin domain containing 1(VSIG1) and CD44. RESULTS The positivity rate was 88.75% for SLUG, 83.75% for VSIG1, 36.25% for CD44 and 10% for n-cadherin. no correlation was noted between the examined markers and clinicopathological parameters. nuclear positivity for SLUG and VSIG1 was observed in all cases with distant metastasis. The extra-gastrointestinal stromal tumors(e-GISTs) expressed nuclear positivity for VSIG1 and SLUG, with infrequent positivity for n-cadherin and CD44. The low overall survival was mainly dependent on VSIG1 negativity(P = 0.01) and nuclear positivity for SLUG and/or CD44. COnCLUSIOn GIST aggressivity may be induced by nuclear upregulation of SLUG and loss or cytoplasm-to-nuclear translocation of VSIG1. SLUG and VSIG1 may act as activated nuclear transcription factors. The CD44, but not n-cadherin, might also have an independent prognostic value in these tumors. The role of the EMT/MET-related transcription factors in the evolution of GISTs, should be revisited with a larger dataset. This is the first study exploring the IHC pattern of VSIG1 in GISTs.

关键词：蛞蝓 Glycoprotein A34 n-cadherin 包含胃肠的 stromal 肿瘤的 V 集合和免疫球蛋白领域

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Expression and significance of E-cadherin,n-cadherin,transforming growth factor-β1 and Twist in prostate cancer

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Asian Pacific Journal of Tropical Medicine 2014年第1期7卷 76-82页

作者： Ge-Liang Liu Han-Jie Yang Tian Liu Yun-Zhao Lin Department of Urinary Surgery Pingxiang Hospital Affiliated to Southern Medical University Graduate School Nanchang University Wenzhou Medical University

Objective:To study the expression of E-cadherin,n-cadherin,TGF-|3 1 and Twist protein and investigate its significance in the occurrence and development of prostate ***:The expression of E-cadherin,n-cadherin,TGF-β1 and Twist protein in 59 prostate cancer tissues and 21 adjacent tissues were detected by immunohistochemical SABC staining,and the correlation with clinicopathological features was ***:Positive rates of E-cadherin,n-cadherin,TGF-β1 and Twist were 32.2%,54.2%,71.2%and 74.6%,respectively,in prostate cancer tissues and 85.7%,9.52%,19.0%and 9.52%,respectively,in cancer—adjacent tissues,with significant differences between the two groups(Pn of E-cadherin was related to the differentiation of prostate cancer tissues and PSA level,but was not associated with clinical stage,lymph node metastasis,bony metastasis and *** increased expression of n-cadherin,TGF-β1 and Twist was related to the differentiation of prostate cancer tissues,clinical stage,lymph node metastasis,bony metastasis,but not to *** difference in positive expression of n-cadherin and TGF-β1 was significant between PSA≤20μg/L group and PSA>20μg/L group,but the positive expression of Twist was not significant between *** expression of E-cadherin was highly negatively correlated with that of n-cadherin and also highly negatively correlated with that of Twist The expression of TGF-β1 was correlated with those of E-cadherin,n-cadherin and ***:The reduced expression of E-cadherin,abnormal expression of n-cadherin,transformation form E-cadherin to n-cadherin and the increased expression of TGF-β1 and Twist play an important role in the occurrence and development of prostate cancer.

关键词： Prostatic neoplams E-cadherin n-cadherin TGF-β1 Twist protein Epithelial-mesenchymal transition

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沉默n-cadherin对人牙髓干细胞增殖和迁移能力的影响

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口腔疾病防治 2022年第11期30卷 779-784页

作者：邓子龙闫文娟赵望泓吴补领南方医科大学南方医院口腔科广东广州510515 南方医科大学口腔医学院广东广州510515 南方医科大学深圳口腔医院(坪山)牙体牙髓病科广东深圳518118

目的探讨沉默n-cadherin对人牙髓干细胞(dental pulp stem cells,DPSCs)增殖和迁移能力的影响,为基于DPSCs的牙髓再生提供实验依据。方法采用n-cadherin shRnA慢病毒转染DPSCs,qRT-PCR、Western blot检测n-cadherin的表达水平,验证沉默效率。实验分为阴性对照组(shRnA-nC)和n-cadherin shRnA沉默组。采用CCK-8法检测细胞增殖能力,流式细胞术检测细胞周期和细胞凋亡情况,Transwell法检测细胞迁移能力。结果n-cadherin shRnA可显著降低DPSCs的n-cadherin mRnA和蛋白的表达水平(Pn-cadherin shRnA组细胞增殖活性分别在细胞接种的第3、4天高于shRnA-nC组,第6~8天低于shRnA-nC组,差异均具有统计学意义(Pn-cadherin shRnA组处于S期和G2期的细胞比例大于shRnAnC组(Pn-cadherin shRnA组细胞处于S期和G2期的比例小于shRnA-nC组(Pn-cadherin shRnA组凋亡细胞比例大于shRnA-nC组(Pnswell上室培养20 h,n-cadherin shRnA组穿过Transwell上室小孔的细胞数量均多于shRnA-nC组(Pn-cadherin表达可促进DPSCs早期的增殖和迁移能力。

关键词：牙髓干细胞增殖迁移 n-cadherin 牙髓再生细胞周期细胞凋亡慢病毒微环境

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n-cadherin在急性白血病患者骨髓白血病细胞中的表达及意义

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中国实验血液学杂志 2016年第5期24卷 1312-1318页

作者：马杰刘亚杰张秋堂余庆峰张占芳张梦颖王冲甘思林陈胜梅曹伟杰谢新生刘延方刘林湘万鼎铭王芳孙玲孙慧郑州大学第一附属医院血液科河南郑州450052

目的:探讨神经钙粘蛋白(n-cadherin)在急性白血病患者骨髓白血病细胞中的表达及意义。方法:应用流式细胞术检测n-cadherin在113例急性白血病患者骨髓白血病细胞中的表达并分析其与临床特征及预后的相关性。结果:n-cadherin在急性白血病... 详细信息

目的:探讨神经钙粘蛋白(n-cadherin)在急性白血病患者骨髓白血病细胞中的表达及意义。方法:应用流式细胞术检测n-cadherin在113例急性白血病患者骨髓白血病细胞中的表达并分析其与临床特征及预后的相关性。结果:n-cadherin在急性白血病患者骨髓白血病细胞中的表达存在差异,表达水平波动在0%-99.7%;成人急性髓系白血病患者n-cadherin^+组CD34^+率较n-cadherin^-组显著升高(67.39%vs 33.33%)(P=0.013),两组间1疗程CR率、总CR率及复发率间的差异无统计学意义(P>0.05);急性淋巴细胞白血病患者n-cadherin^+组白细胞数(21.31±7.07 vs 51.10±23.69)(P=0.008)和外周血原始细胞比例〔(43.22±5.75)%vs(66.45±5.65)%(P=0.015)〕显著低于n-cadherin^-组,1疗程CR率和总CR率低于n-cadherin-组,复发率高于n-cadherin-组,但差异无统计学意义(P>0.05);儿童急性淋巴细胞白血病患者n-cadherin^+组CD33^+率较n-cadherin-组显著增高(47.62%vs 0%)(P=0.012),两组间1疗程CR率和总CR率无显著差异。n-cadherin^+组复发率高于n-cadherin^-组(30.00%vs 0%)(P=0.115)。成人AML、非M3-AML、ALL和儿童ALL患者n-cadherin^-组中位生存时间、3年总生存(OS)率和3年无复发生存率均好于n-cadherin^+组,但其差异无统计学意义。结论:n-cadherin在急性白血病患者骨髓白血病细胞中的表达水平与部分临床特征有关,对急性白血病患者的生存有一定影响。

关键词：急性白血病骨髓白血病细胞 n-cadherin 临床意义

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n-cadherin表达下调对THP-1细胞增殖、凋亡和药物敏感性的影响及机制研究

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中华血液学杂志 2018年第6期39卷 514-517页

作者：马杰刘亚杰刘晓艳汤平马平余庆峰张占芳李宁甘思林孙慧郑州大学第一附属医院血液科 450000

神经钙黏蛋白（n-cadherin）是经典的钙黏蛋白超家族成员之一，表达于神经细胞、内皮细胞、肌肉细胞和造血干细胞在内的多种正常组织中。它不仅是胚胎发育过程中原肠胚形成和神经嵴发育的重要分子，而且在结直肠癌、前列腺癌、胃癌、乳... 详细信息

神经钙黏蛋白（n-cadherin）是经典的钙黏蛋白超家族成员之一，表达于神经细胞、内皮细胞、肌肉细胞和造血干细胞在内的多种正常组织中。它不仅是胚胎发育过程中原肠胚形成和神经嵴发育的重要分子，而且在结直肠癌、前列腺癌、胃癌、乳腺癌等实体肿瘤中参与调控肿瘤的浸润和转移、细胞周期和凋亡等病理过程，并与肿瘤的恶性程度和侵袭性呈正相关。

关键词： n-cadherin THP-1 药物敏感性细胞增殖表达下调凋亡胚胎发育过程实体肿瘤

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