上皮间质转化的分子机制研究进展

上皮间质转化(epithelial-mesenchymal transition,EMT)是上皮细胞转化为间质细胞,形成结缔组织或者形成新的上皮组织,这些细胞不会再表达上皮细胞的特性,而是具有间质细胞的形态学和转移的特性,这些特性诱使细胞转移和侵袭。EMT早在上世纪80年代在胚胎发育时发现,目前证明与癌细胞的转移、侵袭存在密切关系[1]。     

上皮-间质转化和多形性成胶质细胞瘤的侵袭性

[摘 要] 多形性成胶质细胞瘤（glioblastoma multiforme,GBM）是最常见的中枢神经系统恶性肿瘤,传统的治疗手段如手术、放 疗和化疗等虽然不断进步,但依然预后不佳。上皮-间质转化（epithelial-interstitial transformation,EMT）是上皮细胞来源的恶性肿 瘤获得侵袭和迁移能力的重要病理过程,与GBM的侵袭、迁移及放化疗耐受性等恶性生物学行为密切相关。本文将聚焦EMT 相关病理生理过程及其与GBM侵袭和转移行为相关的最新进展,阐述EMT在GBM中的基因调控与分子信号通路,如金属基质 蛋白酶、TGF-β和转录因子Snail、Twist等,从而为GBM研究提供新的思路。     

上皮-间质转化与肿瘤耐药性的研究进展

上皮-间质转化（EMT）是上皮细胞表型向间质细胞表型转变的过程,在肿瘤发生及其演变中发挥着重要的作用。近期研究表明,EMT在多种肿瘤的化疗耐药中发挥重要作用,而化疗药物也能增强肿瘤的恶性程度包括诱导EMT表型的产生。本文结合国内外最新报道,对EMT与肿瘤耐药关系的研究进展进行综述。      

上皮样胶质母细胞瘤10例报告并文献复习

背景与目的:上皮样胶质母细胞瘤(epithelioid glioblastoma,EGBM)是一种罕见的胶质母细胞瘤亚型,国内外报道较为少见.探讨EGBM的临床、病理学及影像学特征.方法:回顾性分析2014—2019年在华山医院北院经手术后病理学检查证实的10例EGBM的临床资料,对其临床、病理学及影像学特征进行归纳总...     

MicroRNA与肿瘤上皮-间质转化关系的研究进展

上皮-间质转化(epithelial-mesenchymal transition,EMT)是指上皮细胞通过特定程序转化为具有间质表型细胞的生物学过程,在肿瘤的发生、发展、转移中发挥重要作用。microRNA(miRNA)作为一类长度为19-25个核苷酸的短链非编码RNA,是转录后调控网络中重要的调控因子,与肿瘤EMT相关基因表达之间关系密切,已成为肿瘤领域的研究热点。现对近年来miRNA与肿瘤EMT关系的研究进展做一综述。     

宫颈癌上皮-间质转化的研究进展

宫颈癌是常见的妇科恶性肿瘤之一,严重威胁着妇女的健康,且发病率近几年来趋于年轻化。尽管使用了先进的筛查方法和预防性疫苗,但在治疗方案极为有限和副作用严重的情况下,超过一半的宫颈癌病例被诊断为晚期。如何解决上述问题,需从分子生物学层面来更好的认识宫颈癌。其中上皮-间质转化（epithelial-mesenchymal transition,EMT）是近年来研究的热点,EMT是由上皮细胞表型向间质细胞表型转变的可逆的生物学过程,EMT可促进宫颈癌细胞的迁移、侵袭,进而促进肿瘤的转移,影响患者的预后。本文综合目前的研究进展,将对近年来宫颈癌的EMT相关研究进展作一综述。     

ZDHHC12在胶质母细胞瘤中通过YAP1调控肿瘤特性

背景和目的:胶质母细胞瘤(glioblastoma,GBM)是目前常见的恶性脑部肿瘤之一,但GBM相关发病机制仍不完全清楚。本研究旨在分析锌指DHHC结构域蛋白(zinc finger DHHC domain-containing protein,ZDHHC)12对Yes相关蛋白1(Yes-associated protein 1,YAP1)的调控,以及ZDHHC12/YAP1轴对GBM肿瘤特性的调控。方法:在癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库以及基因型-组织表达(Genotype-Tissue Expression,GTEx)数据库中分析ZDHHC12分别在正常脑组织及GBM中的表达情况,运用蛋白质印迹法(Western blot)以及实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测,分析在U87、U251以及人正常星形胶质细胞(NHA)的mRNA表达及蛋白水平。在U87和U251两种GBM细胞系中通过设计的小干扰R...     

β-catenin在膀胱癌上皮-间质转化中的作用及相关机制

目的:探讨β-catenin在膀胱癌上皮-间质转化(epithelial-mesenchymal transition,EMT)过程中的作用以及相关分子机制。方法:利用siRNA靶向沉默膀胱癌细胞系T24细胞的β-catenin基因,并利用Real-time quantitative PCR和Western blot实验验证siRNA敲减效率。通过Transwell实验检测β-catenin敲减后T24细胞的侵袭能力,进一步使用Real-time quantitative PCR和Western blot实验检测β-catenin敲减后T24细胞的EMT相关标志物的变化。最后,通过下载TCGA数据库,并分析β-catenin与EMT相关标志物的相关性。结果:我们成功在mRNA和蛋白水平上沉默了β-catenin。通过Transwell实验发现,与对照组相比,β-catenin敲减组细胞的侵袭能力下调。与对照组相比,β-catenin敲减组的Slug蛋白、Vimentin蛋白和mRNA下调,E-cadherin蛋白和mRNA上调。通过分析TCGA数据库发现,β-catenin与Slug（r=0.183 5,P=0.000 2）和Vimentin (r=0.190 3,P=0.000 1)均呈正相关。结论:β-catenin通过调控Slug的表达从而调控膀胱癌细胞的EMT。     

上皮间质转化在卵巢癌进展及化疗耐药中的研究进展

卵巢癌是致死性最高的妇科恶性肿瘤,居全球女性因癌症死亡原因第8位,其预后差的主要原因是就诊时已处于疾病的晚期,且迅速对化疗产生耐药。越来越多的证据表明,上皮间质转化（epithelial-to-mesenchymal transition,EMT）在卵巢癌的进展中发挥重要作用,并且促进化疗耐药。本文将重点探讨EMT在卵巢癌进展过程中各环节所发挥的作用,同时对EMT介导的不同类型的化疗耐药机制进行探讨。     

Inhibition of histamine receptor 3 suppresses glioblastoma tumor growth,invasion, and epithelial-to-mesenchymal transition

Histamine receptor 3 (H3R) is expressed in various tumors and correlated with malignancy and tumor proliferation. However, the role of H3R in tumor invasion and epithelial to mesenchymal transition (EMT) remains unknown. Here, we explored the H3R in the highly invasive glioblastoma (GBM) and U87MG cells. We found that H3R mRNA and protein levels were up-regulated in the GBM and glioma cell lines compared to normal brain tissue and astrocytes. In U87MG cell line, inhibition of H3R by siRNA or the antagonist ciproxifan (CPX) suppressed proliferation, invasiveness, and the expression of EMT activators (Snail, Slug and Twist). In addition, expression of epithelial markers (E-cadherin and ZO-1) was up-regulated and expression of mesenchymal markers (vimentin and N-cadherin) was down-regulated in vitro and in vivo in a xenograft model. In addition, we also showed that inhibition of H3R by siRNA or CPX inactivated the PI3K/Akt and MEK/ERK signaling pathways, while inhibition of Akt or ERK activity with antagonists or siRNAs suppressed H3R agonist (R)-(α)-(−)- methylhistamine dihydrobromide (RAMH) mediated invasion and reorganization of cadherin-household. In conclusion, overexpression of H3R is associated with glioma progression. Inhibition of H3R leads to suppressed invasion and EMT of GBM by inactivating the PI3K/Akt and MEK/ERK pathways in gliomas.     

Chemoradiation induces epithelial-to-mesenchymal transition in esophageal adenocarcinoma

Multimodality treatment has advanced the outcome of esophageal adenocarcinoma (EAC), but overall survival remains poor. Therapeutic pressure activates effective resistance mechanisms and we characterized these mechanisms in response to the currently used neoadjuvant treatment against EAC: carboplatin, paclitaxel and radiotherapy. We developed an in vitro approximation of this regimen and applied it to primary patient-derived cultures. We observed a heterogeneous epithelial-to-mesenchymal (EMT) response to the high therapeutic pressure exerted by chemoradiation. We found EMT to be initiated by the autocrine production and response to transforming growth factor beta (TGF-β) of EAC cells. Inhibition of TGF-β ligands effectively abolished chemoradiation-induced EMT. Assessment of TGF-β serum levels in EAC patients revealed that high levels after neoadjuvant treatment predicted the presence of fluorodeoxyglucose uptake in lymph nodes on the post-chemoradiation positron emission tomography-scan. Our study shows that chemoradiation contributes to resistant metastatic disease in EAC patients by inducing EMT via autocrine TGF-β production. Monitoring TGF-β serum levels during treatment could identify those patients at risk of developing metastatic disease, and who would likely benefit from TGF-β targeting therapy.     

A comparison of epithelial-to-mesenchymal transition and re-epithelialization

Wound healing and cancer metastasis share a common starting point, namely, a change in the phenotype of some cells from stationary to motile. The term, epithelial-to-mesenchymal transition (EMT) describes the changes in molecular biology and cellular physiology that allow a cell to transition from a sedentary cell to a motile cell, a process that is relevant not only for cancer and regeneration, but also for normal development of multicellular organisms. The present review compares the similarities and differences in cellular response at the molecular level as tumor cells enter EMT or as keratinocytes begin the process of re-epithelialization of a wound. Looking toward clinical interventions that might modulate these processes, the mechanisms and outcomes of current and potential therapies are reviewed for both anti-cancer and pro-wound healing treatments related to the pathways that are central to EMT. Taken together, the comparison of re-epithelialization and tumor EMT serves as a starting point for the development of therapies that can selectively modulate different forms of EMT.     

Epithelial-to-mesenchymal(-like) transition as a relevant molecular event in malignant gliomas

Tumor dissemination and metastatic behavior account for the vast majority of cancer associated mortality. Epithelial tumors achieve this progressive state via epithelial-to-mesenchymal transition (EMT); however, the importance of this process in the neuroepithelial context is currently very controversially discussed. The review describes the current research status concerning EMT-like changes in malignant gliomas including the role of TWIST1, ZEB1/ZEB2 and SNAIl1/SNAIl2 as inducers for cell-invasiveness in GBMs. Furthermore, WNT/β-catenin signaling with its key-component FRIZZLED4 activating an EMT-like program in malignant gliomas and its relationship to the stem-like phenotype as well as discoveries on micro-RNA-level regulating the EMT-like process are discussed.     

组蛋白密码与胶质母细胞瘤关系的研究进展

组蛋白密码由组蛋白中被修饰氨基酸的种类、位置和修饰类型构成。目前研究发现组蛋白密码与胶质母细胞瘤（glioblastoma ,GBM）密切相关。GBM细胞中各种效应蛋白与组蛋白修饰后相应靶位点的结合效应控制着染色质的状态,进一步影响GBM细胞DNA 复制及基因表达调控等表观遗传现象。GBM组蛋白密码信息存在于包括组蛋白乙酰化、甲基化、磷酸化、泛素化等翻译修饰过程中。组蛋白密码与GBM关系的研究为GBM的发生发展、临床诊断和治疗研究提供了更多分子靶点。