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CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly
Wangkai Xie Chao Chen Zheng Han Jingjing Huang Xin Liu Hongjun Chen Teming Zhang Sian Chen Chenbin Chen Mingdong Lu Xian Shen Xiangyang Xue 《Molecular carcinogenesis》2020,59(4):339-352
Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC. 相似文献
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目的:采用蛋氨酸灌胃复制高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)致内皮功能障碍,在此基础上,联合脂多糖(lipopolysaccharide,LPS)和角叉菜胶(carrageenan,Ca)造成大鼠体内广泛微血栓形成,观察血管内皮损伤和功能障碍对大鼠体内微血栓形成的促进作用。方法: ①内皮损伤模型的建立。SD大鼠随机分为对照组(control)、内皮功能障碍组(HHcy)。HHcy组采用蛋氨酸灌胃4周复制HHcy致内皮功能障碍模型,对照组以等量纯净水灌胃。4 周后检测血浆同型半胱氨酸(homocysteine,Hcy)水平,并取大鼠胸主动脉段进行血管舒张功能检测,同时检测血浆一氧化氮(NO)和血管性假血友病因子(von Willebrand factor,vWF)水平,以评价血管内皮功能状况。②Ca/LPS诱导微血栓形成。SD大鼠随机分为对照组(control)、微血栓组(Ca/LPS)、内皮功能障碍加微血栓组(HHcy+Ca/LPS)。Ca/LPS组大鼠腹腔注射Ca,16 h再腹腔注射LPS。注射LPS 20 h后心脏采血检测凝血功能和血小板计数,镜下观测肠系膜微循环,24 h大鼠颈动脉采血结束实验,检测血浆NO和vWF值。对照组腹腔注射等量生理盐水,检测指标同模型组。HHcy+Ca/LPS组大鼠经蛋氨酸灌胃持续4周后,再按照上述方法注射Ca/LPS,观察内皮功能障碍对大鼠微循环障碍和微血栓形成的影响。结果: ①蛋氨酸灌胃4周导致HHcy,血浆vWF水平显著升高,NO水平降低,内皮依赖性血管舒张功能显著降低,提示血管内皮功能受损,大鼠内皮功能障碍模型复制成功。②Ca/LPS组肠系膜微循环可见广泛微血栓形成,注射LPS后20 h ,通过检测凝血指标可见血液处于高凝状态。而与之比较,HHcy+Ca/LPS组微循环障碍进一步加强,血小板计数减少,血浆NO值降低,vWF升高;注射LPS 20 h后可见血液处于继高凝状态之后的消耗性低凝状态。结论: 蛋氨酸灌胃4周导致HHcy,诱导血管内皮功能障碍。联合Ca/ LPS 造模可建立微循环障碍和微血栓形成的动物模型,而内皮功能障碍能加速加重微循环障碍和微血栓形成。 相似文献
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《结合医学学报(英文版)》2023,21(3):268-276
ObjectiveAlthough there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.MethodsSmall interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2′-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.ResultsJAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.ConclusionJAML is a novel target for kaempferol against LUAD cells.Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268–276. 相似文献
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根据TNFα转换酶(TNFαconvertingenzyme,TACE)cDNA序列和TACE分子结构特征设计并合成引物,采用逆转录PCR(RT-PCR)技术,首次从健康人脾贴壁细胞中扩增出TACEcDNA解整合素结构片段(disintegrindomain),并用大肠杆菌脂多糖(LPS)刺激人脾贴壁细胞,观察其对TACEmRNA表达的调节作用。结果表明不同健康人脾贴壁细胞中均存在TACEmRNA的自然表达,并且LPS对该表达具有上调作用,其上调程度与LPS刺激时间呈正比关系。 相似文献
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《Explore (New York, N.Y.)》2023,19(3):283-289
The steroid hormone cortisol can be used to measure physiological stress in humans. The hypothalamic-pituitary-adrenal (HPA) axis synthesizes cortisol, and a negative feedback cycle regulates cortisol depending on an individual's stress level and/or circadian rhythm. Chronic stress of college undergraduate students is associated with various adverse health effects, including anxiety and depression. Reports suggest that stress levels have risen dramatically in recent years, particularly among university students dealing with intense academic loads in addition to COVID-19 pandemic-related uncertainty. The increasing rate of mental illness on college campuses necessitates the study of mediators potentially capable of lowering stress, and thus cortisol levels. Research on mediation techniques and coping mechanisms have gained traction to address the concerning levels of stress, including the employment of human-animal interaction sessions on college campuses. In this study, human-canine interaction as a stress mediation strategy for undergraduate students was investigated. We measured salivary cortisol levels in 73 college undergraduate students during a 60-min interaction period with a dog to determine whether human-canine interactions are effective in lowering cortisol levels and potentially reducing chronic stress typical of undergraduate students. Our results indicate that a human-canine interaction for 60 min is an effective method for significantly reducing salivary cortisol and stress levels among undergraduate college students. These findings support the expansion of animal visitation programs on college campuses to help students manage stress. 相似文献
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Clinical and experimental study on treatment of acute cerebral infarction with Acanthopanax Injection 下载免费PDF全文
AlotofclinicalmaterialofintegratedtraditionalChineseandwesternmedicine(TCMWM)indicatedthatthemainpathologicalchangeofcerebralischemicapoplexyis“TheblockageofCollateralsbybloodstasisresultedfromQi,whichisunabletopromoteblood”.AcanthopancisSeniticosi(R… 相似文献
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Thereexistdifferentdegreesofpathophysi ologicchangesinthetissuesaroundhemorrhagefocusafteracutecerebralhemorrhage[1 ] .Cere bralhemorrhageoftenleadstodysfunctionoftheneuronsinthebrain ,manifestingabnormalelec tricalactivity .Followingacutecerebralhemor rhage,duetotheoppressionofthehematomaandthetoxiceffectofthebloodcontentsaswellaschangesofthemicro environmentaroundthehemorrhagefocus,theelectricalactivityofthecerebralneuronsissuppressedatdifferentde grees.Electroacupuncture (EA)therapyworkell… 相似文献
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