修回日期: 2012-07-13
接受日期: 2012-07-20
在线出版日期: 2012-08-18
侵袭转移是造成消化系恶性肿瘤患者预后不良的主要原因之一. 而肿瘤细胞的运动和迁徙能力在肿瘤的侵袭转移过程中起到了重要作用. Fascin-1是一种肌动蛋白结合蛋白, 其主要功能是在细胞突起内形成平行束结构, 并参与细胞黏附、移动以及信号转导等. 体外实验发现过表达Fascin-1能够增加细胞的侵袭和迁移能力, 而抑制Fascin-1的表达则能够降低细胞的侵袭转移. 在许多消化系恶性肿瘤组织中, 研究发现Fascin-1的上调表达与预后不良, 肿瘤的低分化, TNM分期以及淋巴结和远处器官转移密切相关. 因此Fascin-1可能作为消化系恶性肿瘤新的预后预测分子及肿瘤侵袭转移可能的治疗靶点.
引文著录: 周亮, 王德盛. Fascin-1与消化系恶性肿瘤. 世界华人消化杂志 2012; 20(23): 2125-2130
Revised: July 13, 2012
Accepted: July 20, 2012
Published online: August 18, 2012
Invasion and metastasis are major reasons for poor prognosis of digestive system carcinomas. Motility and migratory capacity are important in contributing to tumor cell invasion and metastasis. Fascin-1 is a globular actin crosslinking protein that can form parallel actin bundles in cell protrusions and is involved in cell adhesion, movement, and signal transduction. In vitro up-regulation of Fascin-1 can increase migration and invasion capacity of cells, while down-regulation of Fascin-1 can decrease migration and invasion capacity of cells. Many studies show that up-regulation of Fascin-1 expression is significantly associated with worse prognosis, poorer differentiation, advanced TNM stage, lymph node metastasis, and distant metastasis in patients with digestive system carcinomas. Therefore, Fascin-1 may have prognostic value as an early biomarker for more aggressive digestive system carcinomas and may be a potential therapeutic target for tumor invasion and metastasis.
- Citation: Zhou L, Wang DS. Fascin-1 and digestive system carcinomas. Shijie Huaren Xiaohua Zazhi 2012; 20(23): 2125-2130
- URL: https://www.wjgnet.com/1009-3079/full/v20/i23/2125.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v20.i23.2125
运动和迁移能力对于肿瘤细胞来说十分重要, 因为他们决定了肿瘤细胞的侵袭和转移潜能. 肿瘤细胞获得高迁移能力的一个重要途径就是通过重组细胞骨架来形成促进细胞运动的结构如伪足[1]. Fascin-1是一种肌动蛋白(actin)结合蛋白, 他能够通过聚合肌动蛋白催化其成束而改变细胞骨架, 使细胞膜表面突起增多, 从而增加上皮细胞的运动性, 同时他能降低细胞与细胞、细胞与细胞外基质的黏附, 降低细胞间联系的完整性, 从而加快细胞的迁移, 促进肿瘤细胞的侵袭与转移[2,3]. 正常条件下, Fascin-1主要分布在正常的间质细胞、内皮细胞、树突状细胞和神经细胞, 但在正常上皮细胞中不表达[4]. 但是在许多肿瘤中都能发现Fascin-1的表达上调, 如肺癌[5]、膀胱癌[6]、乳腺癌[7]、食管癌[8]、胰腺癌[9]、结肠癌[1]、卵巢癌[10]和胃癌[11]. 进一步研究发现上调Fascin-1的表达能够增加肿瘤细胞的侵袭转移能力, 其上调表达也与许多肿瘤的预后不良密切相关[4,5]. 所以Fascin-1有望成为肿瘤新的预后预测分子和可能作为肿瘤侵袭转移的治疗靶点. 本文就Fascin-1在消化系肿瘤中的研究现状和进展作一综述.
在20世纪70年代, 从海胆的卵母细胞质中纯化出一种分子量为55 kDa的肌动蛋白结合蛋白, 即Fascin, 他能与F-actin紧密结合并稳定成束状结构[12,13]. 目前已知的人类Fascin有3种不同形式, 即 Fascin-1, 通常简称为Fascin, 基因定位于染色体7q22, 主要分布在间质组织和神经系统中; Fascin-2基因定位于染色体17q25, 主要在视网膜细胞中表达; Fascin-3基因定位于染色体7q31, 在睾丸中特异表达[2-4]. Fascin基因在11-50之间的氨基酸残基高度保守, 其中第39位的丝氨酸, 为蛋白激酶C的磷酸化位点. Fascin蛋白属于β-三叶虫蛋白质族, 在结构上由4个β-三叶虫结构域组成, 以β-三叶虫折叠为特征[14]. Fascin的主要功能是与F-actin结合, 并使其平行排列呈束状, 而Fascin则定位于束的核心, 这样能够使细胞形成伪足样结构, 从而增加细胞的运动和迁移能力[15]. 最早关于Fascin-1表达和细胞内定位的研究是在脊椎动物细胞中进行的, Fascin-1在不同的细胞类型中表达不同. Fascin-1在T细胞和许多上皮细胞中不表达或者低表达; 而在神经细胞、胶质细胞、骨骼肌细胞、平滑肌细胞、内皮细胞以及一些上皮性肿瘤中呈高表达[16-19]. 通过对体外培养的侵袭性肿瘤细胞的研究, 发现Fascin主要分布在具有运动能力或有丝分裂后的细胞膜边缘的微绒毛和皱褶中[18,20-22]. 而在Fascin-1阳性表达的上皮肿瘤细胞系中, 还发现其位于细胞与细胞之间的黏着连接区[23]. 在上皮细胞中, 过表达的Fascin-1与细胞之间的黏着连接分解相关, Fascin-1通过影响β-连环素(β-catenin)在钙黏素(cadherin)-连环素中的功能, 从而降低细胞间的黏附活性[20,23,24]. 这些说明Fascin-1不仅参与细胞迁移结构的形成, 还参与细胞与细胞之间的黏附, 从而提示Fascin-1在细胞的侵袭转移中可能也起到一定的作用. 但是关于Fascin-1在肿瘤中上调表达的具体机制尚不明确. 研究发现在不同的肿瘤中, 调控Fascin-1上调的机制不同. 在乳腺癌中, Fascin-1可能是c-erbB-2的效应蛋白, c-erbB-2可通过活化NF-γB和TATA核心因子激活Fascin-1基因的转录[21]. 而在食管癌中还发现, 转录因Sp1能够通过直接绑定与Fascin-1的启动子直接调控Fascin-1的表达. 转录因Sp1上调则Fascin-1表达上调, 反之亦然. ERK1/2的特异性抑制剂能够降低转录因Sp1的磷酸化水平从而抑制Fascin-1基因的转录, 造成表达下调. 刺激表皮生长因子(epidermal growth factor, EGF)的表达能够通过活化ERK1/2通路来增加转录因Sp1的磷酸化水平, 从而增加Fascin-1的表达[25]. 除此之外, TNF-α[26]、Wnt[27]和IL-6[28]等信号通路亦能上调Fascin-1的表达. 所以关于Fascin-1在肿瘤中的调控机制尚需进一步研究.
口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)是最常见的头颈部肿瘤之一, 其易复发并伴有很高的转移从而造成预后不良. 从OSCC临床标本中观察到, Fascin-1的过表达与淋巴结转移、肿瘤复发以及总体生存率差密切相关[29,30]. 而体外研究发现在培养的OSCC细胞中, 采用siRNA的方法下调Fascin-1的表达能够直接造成细胞表面伪足减少, 细胞间黏附性增加, 从而抑制细胞的侵袭转移. 同时下调Fascin-1表达能够不同程度的增加E-cadherin、β-catenin和Twist的表达[31]; 类似的实验发现Fascin-1的表达水平与OSCC细胞的侵袭能力相关. Fascin-1的表达与E-cadherin的表达成负相关, 过表达Fascin-1能够通过下调E-cadherin来提高OSCC细胞的侵袭能力[29]. 而E-cadherin、β-catenin和Twist与上皮间质转化(epithelial-mesenchymal transition, EMT)关系密切. 同时Fascin-1能够通过增加磷酸化的AKT, ERK1/2和JNK1/2来激活AKT和MAPK通路参与OSCC的发展过程[30]. 因此, 这些结果都提示在OSCC中, Fascin-1在调节肿瘤的发展和EMT过程中发挥了重要作用.
免疫组织化学的结果显示Fascin-1在食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)中的表达比正常食管上皮高. 单因素分析显示Fascin-1的高表达与预后不良, 低分化, T4分期, 淋巴结以及远处转移密切相关[32,33]. 多因素分析提示Fascin-1蛋白的表达可以作为食管癌独立的预后预测分子[8]. Fascin-1阳性表达的食管癌患者5年生存时间明显低于未表达者[33]. 体外实验显示在KYSE170细胞中(一种Fascin-1过表达细胞)由于Fascin-1表达下调, 细胞的运动和侵袭能力明显下调[34]. 而Fascin-1对食管癌细胞侵袭的影响可能与金属蛋白酶(matrix metalloproteases, MMP)如MMP-2和MMP-9的活性相关[35]. 而在永生化的食管上皮细胞中上调Fascin-1的表达, 能够加速细胞的增殖和侵袭[36]. 并且在食管癌细胞中发现microRNAs (miRNAs)-143、miR-145和miR-133能够通过调控Fascin-1来参与食管癌的发生及转移[37,38]. 在探讨Fascin-1调控细胞侵袭转移的机制中, 发现恢复基因中含半胱氨酸61(cysteine-rich 61, CYR61)或者结缔组织生长因子(connectire tissue growth factor, CTGF)能够逆转由于Fascin下调所造成的细胞增殖和侵袭能力抑制. 在ESCC中CYR61和CTGF蛋白上调表达, 并且与Fascin-1过表达相关. Fascin-1能够通过转化生长因子-β通路来改变CYR61和CTGF的表达[36].
胃癌是最常见的消化系肿瘤之一, 淋巴结转移是胃癌预后不良的主要原因之一. 通过免疫组织化学的方法, 观察到Fascin-1在胃癌组织中的表达高于正常组织[39]; Fascin-1在胃癌和胃腺瘤中的表达高于临近的非肿瘤组织, 而且在低分化的胃癌中Fascin-1蛋白呈中强度表达[11]. 体外实验提示不同侵袭能力的胃癌细胞中Fascin-1的表达不同, 下调Fascin-1能够改变肿瘤细胞形态, 并且降低细胞的运动和侵袭能力[39]. 通过对比临床病理资料, 发现Fascin-1的阳性表达与年龄, 浆膜侵犯, 淋巴结转移, 病例学分级, TNM分期和肿瘤复发密切相关[11,40]. Fascin-1阳性表达的患者总体生存率明显低于Fascin-1阴性表达的患者[41]. 这些都提示Fascin-1可能与胃癌的侵袭转移密切相关, 并且可作为胃癌预后评估的独立分子.
免疫组织化学的结果显示Fascin-1在正常结肠上皮中不表达, 而在结肠癌标本中呈现大量表达[42]. 在肿瘤组织中心和侵袭边缘, Fascin-1的表达比率更高[43]. 在体外培养的结肠癌细胞中上调Fascin-1的表达能够增加细胞的侵袭和转移, 并且能够造成细胞在体内扩散和转移; 而抑制Fascin-1表达则能够降低细胞的侵袭. 有趣的是尽管在原发肿瘤中Fascin-1蛋白的表达与转移相关, 但是Fascin-1在转移灶内并不表达. 当肿瘤细胞到达转移部位时Fascin-1表达下调, 细胞侵袭停止, 增殖能力提高[44]. 这提示Fascin-1在肿瘤的侵袭转移过程中起到重要的作用. 临床研究显示在三期的结肠癌患者中, Fascin-1阳性表达者的5年生存率明显降低, 而远处复发率明显增加[45]. Fascin-1能够独立于TNM分期来预测患者的预后[43,45]. 因此Fascin-1可以作为一个很好的结肠癌侵袭预测的生物标记.
Iguchi等[46]采用免疫组织化学的方法发现肝癌组织中Fascin-1大量表达, 并且Fascin-1表达的肝癌组织比不表达Fascin-1的肝癌组织分化更差. 在Fascin-1阳性表达的肝癌中, 门静脉侵犯, 胆管侵犯及肝内转移更常发生. 另外, 在肝癌中高甲胎蛋白(alpha-fetoprotein, AFP)的表达与Fascin-1表达密切相关, 这些研究说明Fascin-1与肝癌的侵袭转移关系密切. 结合临床病历资料及患者生存时间分析显示, Fascin-1阳性表达的肝癌患者较阴性表达者, 预后更加不良且生存时间明显缩短[47], Fascin-1可以作为肝癌患者预后的独立预测分子[46]. 在探讨Fascin-1参与肝癌侵袭转移的机制的实验中, 发现Fascin-1表达的肝癌组织常伴有E-cadherin的下调. 体外实验发现, 肝癌细胞系HLE细胞呈Fascin-1高表达同时E-cadherin低表达, 细胞侵袭能力明显增加. 在HLE细胞中敲除Fascin-1能够显著抑制细胞的侵袭同时增加E-cadherin的表达. 而另一种肝癌细胞系Huh7细胞Fascin-1低表达和E-cadherin高表达. 在该细胞中上调Fascin-1的表达后侵袭能力增加不明显并且E-cadherin表达不受抑制, 说明Fascin-1不可能独立的诱导侵袭或EMT过程. 但是上调Fascin-1的表达能够通过另外一种机制明显增加Huh7的侵袭潜力. 该机制是MMP-2和MMP-9卷入了Fascin-1调控侵袭转移的过程. 仅仅在HLE细胞中发现MMP大量分泌, 而在Fascin-1过表达的Huh7细胞中MMP分泌增加不多. 将Fascin-1过表达的Huh7细胞与HLE细胞共培养, 发现Huh7细胞的侵袭能力明显增加, 并且可以通过MMP抑制剂抑制该过程. 说明在肝癌细胞中Fascin-1伴随EMT过程促进肝癌的迁移过程而通过MMPs促进细胞的侵袭[48]. 上述研究也说明Fascin-1不仅能够作为肝癌预后的预测分子而且可能作为针对肝癌侵袭转移的作用靶点.
关于Fascin-1在胆道肿瘤中研究较少, 有限的研究发现Fascin-1在正常胆管上皮中不表达或偶尔表达, 而在胆管癌中呈高表达[49]. Fascin-1主要分布在胆管癌细胞的细胞膜和细胞质中. 从原位胆囊癌到浸润性胆囊癌及胆管癌中都能观察到Fascin-1的高表达, 这说明Fascin-1参与了肿瘤的发展过程[50]. 而且Fascin-1的高表达与肿瘤的低分化密切相关; 在低分化的肝内胆管癌中, 大的肿瘤(>5 cm)往往伴有高的Fascin-1表达, Fascin-1高表达的患者往往预后不良, 所以Fascin-1可以作为胆道肿瘤独立的预测分子[49].
Yamaguchi等[51]在切除的胰腺癌组织中观察到Fascin-1大量表达, Fascin-1在肿瘤边缘及肿瘤中表达明显高于非肿瘤组织, 但是在肿瘤边缘及肿瘤中的表达并没有明显差异. 在肿瘤亚分型中, 肠型肿瘤比胃型肿瘤更多的表达Fascin-1. Fascin-1 mRNA在中低分化的肿瘤中表达比高分化的肿瘤高[51]. 还有研究显示过表达的Fascin-1主要局限于肿瘤的细胞膜和细胞质中, Fascin-1在胰腺肿瘤从原位到侵袭性肿瘤的转化过程中表达逐渐增高[50]. 在胰腺癌细胞系MIA PaCa-2中上调Fascin-1的表达, 结果发现该细胞的移动和转移能力明显增加. 并且将上调Fascin-1的胰腺癌细胞进行裸鼠体内试验发现, 该细胞成瘤虽稍慢, 但是侵袭转移能力明显增强[52], 其具体机制尚不明. 这些研究提示Fascin-1与胰腺癌的发生展过程密切相关.
肿瘤细胞的侵袭转移是消化系肿瘤普遍存在的现象, 其与患者的预后密切相关. 细胞的微结构改变尤其是细胞的骨架的改变在肿瘤发生、发展过程中起到重要作用. Fascin-1作为一种肌动蛋白结合蛋白, 在调控细胞的形态和功能方面起到了十分重要的作用, 而对Fascin-1的研究则是对细胞骨架和生物学研究的扩展. 随着对Fascin-1在消化系肿瘤中的研究逐渐深入, 发现高表达的Fascin-1与患者的预后, 肿瘤的分化、转移密切相关, 而体外实验发现抑制Fascin-1能够通过不同的途径有效降低肿瘤细胞的侵袭转移过程. 因此Fascin-1作为一种消化系肿瘤预后预测分子前景广阔; 鉴于Fascin-1参与了不同肿瘤的侵袭转移过程, 因此其可能作为肿瘤侵袭转移的治疗靶点. 但关于Fascin-1在肿瘤中的作用仍需进一步的研究.
Fascin-1是一种肌动蛋白结合蛋白, 其主要功能是在细胞突起内形成平行束结构, 并参与细胞黏附、移动以及信号转导等. 目前研究发现Fascin-1参与许多肿瘤的侵袭转移过程, 并与患者的预后密切相关.
禹正杨, 副教授, 南华大学附属第一医院
关于Fascin-1在恶性肿瘤中上调的机制以及其促进肿瘤细胞侵袭转移的机制尚待进一步研究.
许多报道提出Fascin-1与肿瘤的转移密切相关, Fascin-1阳性表达的肿瘤患者生存率明显低于未表达者.
Fascin-1作为一种消化系恶性肿瘤预后预测分子前景广阔；鉴于Fascin-1参与了不同消化系恶性肿瘤的侵袭转移过程, 因此其可能作为肿瘤侵袭转移的治疗靶点.
本文对Fascin-1与消化系恶性肿瘤的关系作了较详细的综述, 对基础研究有一定指导意义.
编辑:李军亮 电编:鲁亚静
| 1. | Jawhari AU, Buda A, Jenkins M, Shehzad K, Sarraf C, Noda M, Farthing MJ, Pignatelli M, Adams JC. Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. Am J Pathol. 2003;162:69-80. [PubMed] [DOI] |
| 2. | Adams JC. Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol. 2004;16:590-596. [PubMed] [DOI] |
| 3. | Hashimoto Y, Skacel M, Adams JC. Roles of fascin in human carcinoma motility and signaling: prospects for a novel biomarker? Int J Biochem Cell Biol. 2005;37:1787-1804. [PubMed] [DOI] |
| 4. | Kureishy N, Sapountzi V, Prag S, Anilkumar N, Adams JC. Fascins, and their roles in cell structure and function. Bioessays. 2002;24:350-361. [PubMed] [DOI] |
| 5. | Pelosi G, Pastorino U, Pasini F, Maissoneuve P, Fraggetta F, Iannucci A, Sonzogni A, De Manzoni G, Terzi A, Durante E. Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer. Br J Cancer. 2003;88:537-547. [PubMed] [DOI] |
| 6. | Tong GX, Yee H, Chiriboga L, Hernandez O, Waisman J. Fascin-1 expression in papillary and invasive urothelial carcinomas of the urinary bladder. Hum Pathol. 2005;36:741-746. [PubMed] [DOI] |
| 7. | Yoder BJ, Tso E, Skacel M, Pettay J, Tarr S, Budd T, Tubbs RR, Adams JC, Hicks DG. The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin Cancer Res. 2005;11:186-192. [PubMed] |
| 8. | Hashimoto Y, Ito T, Inoue H, Okumura T, Tanaka E, Tsunoda S, Higashiyama M, Watanabe G, Imamura M, Shimada Y. Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma. Clin Cancer Res. 2005;11:2597-2605. [PubMed] [DOI] |
| 9. | Iacobuzio-Donahue CA, Ashfaq R, Maitra A, Adsay NV, Shen-Ong GL, Berg K, Hollingsworth MA, Cameron JL, Yeo CJ, Kern SE. Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res. 2003;63:8614-8622. [PubMed] |
| 10. | Cao D, Ji H, Ronnett BM. Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary. Int J Gynecol Pathol. 2005;24:67-72. [PubMed] |
| 11. | Hashimoto Y, Shimada Y, Kawamura J, Yamasaki S, Imamura M. The prognostic relevance of fascin expression in human gastric carcinoma. Oncology. 2004;67:262-270. [PubMed] [DOI] |
| 12. | Bryan J, Kane RE. Separation and interaction of the major components of sea urchin actin gel. J Mol Biol. 1978;125:207-224. [PubMed] [DOI] |
| 13. | Otto JJ, Kane RE, Bryan J. Formation of filopodia in coelomocytes: localization of fascin, a 58,000 dalton actin cross-linking protein. Cell. 1979;17:285-293. [PubMed] [DOI] |
| 14. | Ponting CP, Russell RB. Identification of distant homologues of fibroblast growth factors suggests a common ancestor for all beta-trefoil proteins. J Mol Biol. 2000;302:1041-1047. [PubMed] [DOI] |
| 15. | Duh FM, Latif F, Weng Y, Geil L, Modi W, Stackhouse T, Matsumura F, Duan DR, Linehan WM, Lerman MI. cDNA cloning and expression of the human homolog of the sea urchin fascin and Drosophila singed genes which encodes an actin-bundling protein. DNA Cell Biol. 1994;13:821-827. [PubMed] [DOI] |
| 16. | Edwards RA, Bryan J. Fascins, a family of actin bundling proteins. Cell Motil Cytoskeleton. 1995;32:1-9. [PubMed] [DOI] |
| 17. | Adams JC. Formation of stable microspikes containing actin and the 55 kDa actin bundling protein, fascin, is a consequence of cell adhesion to thrombospondin-1: implications for the anti-adhesive activities of thrombospondin-1. J Cell Sci. 1995;108:1977-1990. [PubMed] |
| 18. | Adams JC. Characterization of cell-matrix adhesion requirements for the formation of fascin microspikes. Mol Biol Cell. 1997;8:2345-2363. [PubMed] |
| 19. | Adams JC, Kureishy N, Taylor AL. A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1. J Cell Biol. 2001;152:1169-1182. [PubMed] [DOI] |
| 20. | Yamashiro S, Yamakita Y, Ono S, Matsumura F. Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility of epithelial cells. Mol Biol Cell. 1998;9:993-1006. [PubMed] |
| 21. | Grothey A, Hashizume R, Ji H, Tubb BE, Patrick CW, Yu D, Mooney EE, McCrea PD. C-erbB-2/ HER-2 upregulates fascin, an actin-bundling protein associated with cell motility, in human breast cancer cell lines. Oncogene. 2000;19:4864-4875. [PubMed] [DOI] |
| 22. | Kawano K, Kantak SS, Murai M, Yao CC, Kramer RH. Integrin alpha3beta1 engagement disrupts intercellular adhesion. Exp Cell Res. 2001;262:180-196. [PubMed] [DOI] |
| 23. | Tao YS, Edwards RA, Tubb B, Wang S, Bryan J, McCrea PD. beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex. J Cell Biol. 1996;134:1271-1281. [PubMed] [DOI] |
| 24. | Wong V, Ching D, McCrea PD, Firestone GL. Glucocorticoid down-regulation of fascin protein expression is required for the steroid-induced formation of tight junctions and cell-cell interactions in rat mammary epithelial tumor cells. J Biol Chem. 1999;274:5443-5453. [PubMed] [DOI] |
| 25. | Lu XF, Li EM, Du ZP, Xie JJ, Guo ZY, Gao SY, Liao LD, Shen ZY, Xie D, Xu LY. Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation. Cell Mol Life Sci. 2010;67:3313-3329. [PubMed] [DOI] |
| 26. | Cameron S, Haller F, Dudas J, Moriconi F, Gunawan B, Armbrust T, Langer C, Füzesi L, Ramadori G. Immune cells in primary gastrointestinal stromal tumors. Eur J Gastroenterol Hepatol. 2008;20:327-334. [PubMed] [DOI] |
| 27. | Hölsken A, Buchfelder M, Fahlbusch R, Blümcke I, Buslei R. Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol. 2010;119:631-639. [PubMed] [DOI] |
| 28. | Li R, Li G, Deng L, Liu Q, Dai J, Shen J, Zhang J. IL-6 augments the invasiveness of U87MG human glioblastoma multiforme cells via up-regulation of MMP-2 and fascin-1. Oncol Rep. 2010;23:1553-1559. [PubMed] [DOI] |
| 29. | Lee TK, Poon RT, Man K, Guan XY, Ma S, Liu XB, Myers JN, Yuen AP. Fascin over-expression is associated with aggressiveness of oral squamous cell carcinoma. Cancer Lett. 2007;254:308-315. [PubMed] [DOI] |
| 30. | Alam H, Bhate AV, Gangadaran P, Sawant SS, Salot S, Sehgal L, Dange PP, Chaukar DA, D'cruz AK, Kannanl S. Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma. BMC Cancer. 2012;12:32. [PubMed] [DOI] |
| 31. | Chen SF, Lin CY, Chang YC, Li JW, Fu E, Chang FN, Lin YL, Nieh S. Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells. J Oral Pathol Med. 2009;38:722-730. [PubMed] [DOI] |
| 32. | Hsu KF, Lin CK, Yu CP, Tzao C, Lee SC, Lee YY, Tsai WC, Jin JS. Cortactin, fascin, and survivin expression associated with clinicopathological parameters in esophageal squamous cell carcinoma. Dis Esophagus. 2009;22:402-408. [PubMed] [DOI] |
| 33. | Qin YR, Tang H, Qiao JJ, Li FF, Ai JY. [Expression of fascin in human esophageal squamous cell carcinoma and its clinical significance]. Nanfang Yike Daxue Xuebao. 2011;31:1216-1219. [PubMed] |
| 34. | Xue LY, Hu N, Song YM, Zou SM, Shou JZ, Qian LX, Ren LQ, Lin DM, Tong T, He ZG. Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma. BMC Cancer. 2006;6:296. [PubMed] [DOI] |
| 35. | Xie JJ, Xu LY, Zhang HH, Cai WJ, Mai RQ, Xie YM, Yang ZM, Niu YD, Shen ZY, Li EM. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells. Biochem Biophys Res Commun. 2005;337:355-362. [PubMed] [DOI] |
| 36. | Xie JJ, Xu LY, Wu JY, Shen ZY, Zhao Q, Du ZP, Lv Z, Gu W, Pan F, Xu XE. Involvement of CYR61 and CTGF in the fascin-mediated proliferation and invasiveness of esophageal squamous cell carcinomas cells. Am J Pathol. 2010;176:939-951. [PubMed] [DOI] |
| 37. | Liu R, Liao J, Yang M, Sheng J, Yang H, Wang Y, Pan E, Guo W, Pu Y, Kim SJ. The cluster of miR-143 and miR-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1. PLoS One. 2012;7:e33987. [PubMed] [DOI] |
| 38. | Kano M, Seki N, Kikkawa N, Fujimura L, Hoshino I, Akutsu Y, Chiyomaru T, Enokida H, Nakagawa M, Matsubara H. miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma. Int J Cancer. 2010;127:2804-2814. [PubMed] [DOI] |
| 39. | Kim SJ, Choi IJ, Cheong TC, Lee SJ, Lotan R, Park SH, Chun KH. Galectin-3 increases gastric cancer cell motility by up-regulating fascin-1 expression. Gastroenterology. 2010;138:1035-1045. e1-e2. [PubMed] |
| 40. | Tsai WC, Jin JS, Chang WK, Chan DC, Yeh MK, Cherng SC, Lin LF, Sheu LF, Chao YC. Association of cortactin and fascin-1 expression in gastric adenocarcinoma: correlation with clinicopathological parameters. J Histochem Cytochem. 2007;55:955-962. [PubMed] [DOI] |
| 41. | Li X, Zheng H, Hara T, Takahashi H, Masuda S, Wang Z, Yang X, Guan Y, Takano Y. Aberrant expression of cortactin and fascin are effective markers for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas. Int J Oncol. 2008;33:69-79. [PubMed] |
| 42. | Hashimoto Y, Skacel M, Lavery IC, Mukherjee AL, Casey G, Adams JC. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer. 2006;6:241. [PubMed] [DOI] |
| 43. | Chan C, Jankova L, Fung CL, Clarke C, Robertson G, Chapuis PH, Bokey L, Lin BP, Dent OF, Clarke S. Fascin expression predicts survival after potentially curative resection of node-positive colon cancer. Am J Surg Pathol. 2010;34:656-666. [PubMed] |
| 44. | Vignjevic D, Schoumacher M, Gavert N, Janssen KP, Jih G, Laé M, Louvard D, Ben-Ze'ev A, Robine S. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res. 2007;67:6844-6853. [PubMed] [DOI] |
| 45. | Oh SY, Kim YB, Suh KW, Paek OJ, Moon HY. Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer. J Surg Res. 2012;172:102-108. [PubMed] [DOI] |
| 46. | Iguchi T, Aishima S, Umeda K, Sanefuji K, Fujita N, Sugimachi K, Gion T, Taketomi A, Maehara Y, Tsuneyoshi M. Fascin expression in progression and prognosis of hepatocellular carcinoma. J Surg Oncol. 2009;100:575-579. [PubMed] [DOI] |
| 47. | Huang X, Ji J, Xue H, Zhang F, Han X, Cai Y, Zhang J, Ji G. Fascin and cortactin expression is correlated with a poor prognosis in hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2012;24:633-639. [PubMed] [DOI] |
| 48. | Hayashi Y, Osanai M, Lee GH. Fascin-1 expression correlates with repression of E-cadherin expression in hepatocellular carcinoma cells and augments their invasiveness in combination with matrix metalloproteinases. Cancer Sci. 2011;102:1228-1235. [PubMed] [DOI] |
| 49. | Iguchi T, Aishima S, Taketomi A, Nishihara Y, Fujita N, Sanefuji K, Sugimachi K, Yamashita Y, Maehara Y, Tsuneyoshi M. Fascin overexpression is involved in carcinogenesis and prognosis of human intrahepatic cholangiocarcinoma: immunohistochemical and molecular analysis. Hum Pathol. 2009;40:174-180. [PubMed] [DOI] |
| 50. | Swierczynski SL, Maitra A, Abraham SC, Iacobuzio-Donahue CA, Ashfaq R, Cameron JL, Schulick RD, Yeo CJ, Rahman A, Hinkle DA. Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays. Hum Pathol. 2004;35:357-366. [PubMed] [DOI] |
| 51. | Yamaguchi H, Inoue T, Eguchi T, Miyasaka Y, Ohuchida K, Mizumoto K, Yamada T, Yamaguchi K, Tanaka M, Tsuneyoshi M. Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade. Mod Pathol. 2007;20:552-561. [PubMed] [DOI] |
| 52. | Xu YF, Yu SN, Lu ZH, Liu JP, Chen J. Fascin promotes the motility and invasiveness of pancreatic cancer cells. World J Gastroenterol. 2011;17:4470-4478. [PubMed] [DOI] |