胚胎发育基因Twist与妇科肿瘤研究

胚胎发育基因Twist属于螺旋-环-螺旋蛋白家族中高度保守的转录因子,在肿瘤发生、转移、耐药和血管形成中发挥重要作用,近年来研究发现,妇科肿瘤的发生发展与细胞Twist基因表达异常相关,提示它的激活有可能成为一种新的妇科肿瘤预后判断指标和肿瘤治疗的新靶点.     

TWIST表达与恶性肿瘤转移关系的研究进展

Twist是高度保守的碱性螺旋-环-螺旋转录因子,为新近发现的癌基因.Twist能够编码凋亡抑制蛋白,参与多种上皮来源肿瘤细胞的上皮间充质转化(EMT)过程,调控肿瘤血管、淋巴管的生成等过程,与肿瘤的侵袭、转移关系密切.目前已在多种肿瘤中发现Twist表达增高,开展Twist表达与肿瘤的侵袭转移关联性的研究对临床预防、治疗癌症转移意义重大.     

Twist基因与肿瘤转移和耐药

Twist是碱性螺旋-环-螺旋(bHLH)转录因子家族成员,是上皮间质转化(EMT)过程中的关键调控因子.Twist在胚胎发育及肿瘤的发生发展、侵袭转移过程中发挥重要作用,并与肿瘤耐药密切相关.     

Twist基因介导肿瘤细胞耐药的研究进展

Twist属于高度保守的碱性螺旋-环-螺旋(basichelix-loop-helix,bHLH)结构的转录因子家族,在动物和人的胚胎发育、诱导细胞迁移以及组织塑形中起重要作用.Twist基因具有癌基因特征,在多种恶性肿瘤中高表达,不仅参与肿瘤的发生、侵袭和转移,而且与肿瘤细胞产生耐药性密切相关.Twist基因可以通过抗细胞凋亡、干扰抗微管类药物、诱发上皮-间质转型、诱导产生肿瘤干细胞样特性及影响肿瘤微环境等促使肿瘤细胞耐药,因此有望成为逆转肿瘤耐药的新靶点.     

Twist相关信号通路与肿瘤的研究进展

Twist基因属于碱性螺旋-环-螺旋(basic helix-loop-helix,bHLH)转录因子家族,具有高度保守性,是肿瘤细胞发生间质-上皮转化(epithelial-mesenchymal transition,EMT)并获得迁徙、侵袭和转移能力的主要诱导因子之一,它的信号通路是一个复杂、多途径的网络系统。Twist可通过AKT磷酸化影响口腔鳞癌和膀胱癌的发生和侵袭,通过调控AKT信号途径使鼻咽癌细胞和乳腺癌细胞株产生对紫杉醇的耐药性;STAT3、Twist1和AKT2形成一个功能信号轴参与乳腺癌细胞的侵袭和转移、参与胃癌的发生和发展,异常的p-STAT3/Twist/E-cadherin信号轴可能介导肝癌的侵袭与转移。随着Twist相关信号通路与肿瘤关系的深入研究,其在肿瘤的诊断、治疗和预后预测中的重要作用逐步显现,本文就近年来关于Twist癌基因的结构、功能及其相关信号通路与肿瘤的关系的研究做一综述。     

Twist在上皮性卵巢癌组织中的表达及与临床预后的关系

目的:观察Twist在上皮性卵巢癌组织中的表达情况，分析Twist 阳性表达与上皮性卵巢癌患者铂类耐药、无病生存期的关系。方法:回顾性分析 2011年至2016年西京医院妇科121例手术患者，对其术后石蜡组织标本进行免疫组化染色，分析Twist在正常卵巢组织、肿瘤组织中的表达，在耐药、敏感组中的表达和相关性分析及其与预后的关系。结果:Twist阳性表达率在正常卵巢组织与肿瘤组织中分别为40.00%、60.40%， 其差异有统计学意义(P<0.05)。耐药及敏感组中的上皮性卵巢癌患者中Twist阳性表达率分别为80.00%、52.11%，差异有统计学意义（P<0.05)。上皮性卵巢癌患者中，Twist表达水平越高，患者生存率越低。单因素分析显示:肿瘤复发、FIGO分期、淋巴结转移、铂反应及Twist高表达为影响上皮性卵巢癌患者预后的危险因素；多因素分析显示:复发为上皮性卵巢癌患者的独立预后因素。结论:Twist在上皮性卵巢癌组织中的表达明显高于正常组织，在耐药组的表达明显高于敏感组，但与患者平均无病生存期及总生存期的长短是否也存在统计学差异有待进一步研究。     

上皮-间质转化及其干性作用与肿瘤

上皮-间质转化（EMT）参与肿瘤转移过程,Twist作为关键调控因子在EMT中发挥重要作用,放疗、化疗和多种细胞因子均可诱导Twist介导的EMT。研究表明,肿瘤细胞可能通过EMT转变为肿瘤干细胞样细胞,并进一步导致放化疗抵抗、肿瘤血管形成及远处转移,对肿瘤的预后产生巨大影响,EMT有望成为肿瘤治疗的重要靶点。     

Twist蛋白在胃癌中的表达及其意义

目的 观察上皮-间质转化因子Twist在胃癌中的表达情况及其与病人预后的关系.方法 采用免疫组化S-P法检测59例胃癌组织和15例正常胃黏膜组织中Twist蛋白的表达.结果 59例胃癌组织和15例正常黏膜中Twist阳性率分别为74.6﹪(44/59)和O﹪,Twist蛋白在胃癌组织中的表达水平与病人的年龄、性别、肿瘤的大小及组织的分化程度无关.但与胃癌组织的浸润深度、淋巴结的转移情况、肿瘤的分期以及病人的五年生存情况具有显著相关性.随着胃癌组织浸润深度的加深,Twist蛋白染色阳性率逐渐上升,Twist阳性率增高提示预后不良.结论 Twist蛋白的表达与胃癌侵袭转移有相关关系,并与多种临床病理因素相关,可为胃癌侵袭转移的研究和病人的预后判断提供有价值的参考.     

Twist 对EMT 调控在循环肿瘤细胞监测与抗癌药物评价中的临床意义*

肿瘤细胞的上皮间质可塑性变化包括上皮- 间质化（epithelial-mesenchymal transition ,EMT ）和间质- 上皮转化（mesenchymal-epithelial transition,MET ）的可逆过程,在循环肿瘤细胞（circulating tumor cells ,CTCs）形成、转归及肿瘤转移过程中起到重要作用。Twist在人横纹肌肉瘤、乳腺癌、胃癌等多种肿瘤中过表达,肿瘤细胞中Twist与多种信号通路连接,形成复杂的网状环路参与调控CTCs中EMT/MET的发生并促进肿瘤细胞向远处转移。因此,通过监测CTCs中Twist本身以及所调控的上皮- 间质表型分子标志物的变化,不仅可以增加肿瘤标志物CTCs的检出率,提供肿瘤临床分期及预后评估的直接证据;而且,对于评估多种抗肿瘤药物的疗效及耐药机制均具有重要的临床意义。      

中晚期食管鳞癌组织SOX2和Twist1表达及对放化疗疗效影响

目的 研究SOX2和Twist1在中晚期食管鳞癌组织中表达情况及其与中晚期食管鳞癌同期放化疗疗效的关系.方法 收集2014-04-06-2019-10-27郑州大学附属肿瘤医院收治的40例II～Ⅲ期食管鳞癌患者肿瘤组织及相应的癌旁组织标本,采用免疫组化方法检测SOX2和Twist1表达水平;患者均行同期放化疗,治疗结束...     

Twist is required for thrombin-induced tumor angiogenesis and growth

Twist, a master regulator of embryonic morphogenesis, induces functions that are also required for tumor invasion and metastasis. Because thrombin contributes to the malignant phenotype by up-regulating tumor metastasis, we examined its effect on Twist in five different tumor cell lines and two different endothelial cell lines. Thrombin up-regulated Twist mRNA and protein in all seven cell lines. Down-regulation of Twist in B16F10 tumor cell lines led to a approximately 3-fold decrease in tumor growth on a chorioallantoic membrane assay and approximately 2-fold decrease in syngeneic mice. Angiogenesis was decreased approximately 45% and 36%, respectively. The effect of Twist on angiogenesis was further examined and compared with the effect of thrombin. In studies using a Twist-inducible plasmid, several identical vascular growth factors and receptors were up-regulated approximately 2- to 3-fold in tumor cells as well as human umbilical vascular endothelial cells by both Twist as well as thrombin (vascular endothelial growth factor, KDR, Ang-2, matrix metalloproteinase 1, GRO-alpha, and CD31). Thrombin-induced endothelial cell chemotaxis and Matrigel endothelial cell tubule formation were similarly regulated by Twist. Thus, thrombin up-regulates Twist, which is required for thrombin-induced angiogenesis as measured by endothelial cell migration, Matrigel tubule formation, and tumor angiogenesis.     

Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.

PURPOSE: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with a high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, Twist has been identified to play an important role in EMT-mediated metastasis through the regulation of E-cadherin expression. However, the actual role of Twist in tumor invasiveness remains unclear. The purpose of this study is to investigate the expression and possible role of Twist in HCC. EXPERIMENTAL DESIGN: We evaluated Twist and E-cadherin expression in HCC tissue microarray of paired primary and metastatic HCC by immunohistochemical staining. The role of Twist in EMT-mediated invasiveness was also evaluated in vitro in HCC cell lines. RESULTS: We first showed that overexpression of Twist was correlated with HCC metastasis (P=0.001) and its expression was negatively correlated with E-cadherin expression (P=0.001, r=-0.443) by tissue microarray. A significant increase of Twist at the mRNA level was also found in metastatic HCC cell lines MHCC-97H, MHCC-97L, and H2M when compared with nonmetastatic Huh-7, H2P, and PLC cell lines. The MHCC-97H cell line, which has a higher metastatic ability, was found to have a higher level of Twist than MHCC-97L. Accompanied with increased Twist expression in the metastatic HCC cell lines when compared with the nonmetastatic primary ones, we found decreased E-cadherin mRNA expression in the metastatic HCC cell lines. By ectopic transfection of Twist into PLC cells, Twist was able to suppress E-cadherin expression and induce EMT changes, which was correlated with increased HCC cell invasiveness. CONCLUSION: This study shows that Twist overexpression was correlated with HCC metastasis through induction of EMT changes and HCC cell invasiveness.     

The Effect of Twist Expression on Angiogenesis in Hepatocellular Carcinoma

H epatocellular carcinoma (HCC) has become a worldwide com- mon malignant tumor which shows relatively poor prognosis and rapid progression. Identification of the key molecular targets related to hepatocarcinogenesis has significant therapeutic implicatio…