Introduction: To investigate the roles of fascin in migration and invasiveness in bladder urothelial carcinoma. Materials and Methods: Immunohistochemical detection of fascin in urothelial carcinoma samples and inhibition the expression of fascin in the urothelial carcinoma cell line were performed, then the differences in cell behaviors before and after silencing of the fascin gene were tested. Results: In our study, we found that overexpression of fascin was more frequent in urothelial carcinoma tissues (p < 0.001). Fascin expression was positively correlated with histological grade (p = 0.024) and p T stage (p < 0.001). After transfection of fascin shRNA, the expressions of fascin in 5637 cells and BIU87 cells were efficiently decreased according to real-time RT-PCR and Western blot analysis. When fascin was inhibited, a significant decrease in migration and invasion, and increase in adhesion were observed in 5637 cells and BIU87 cells. However, there was no significant change in the proliferation of 5637 cells or BIU87 cells with or without inhibition of the fascin gene. Conclusions: Fascin expression can be used as a predictor for transformation and progression of urothelial carcinoma, and reduction of fascin levels may represent a novel therapeutic strategy for urothelial carcinoma of the bladder.

Keywords:
Fascin, Urothelial carcinoma, shRNA, Migration, Invasion
1.
Parkin DM: The global burden of urinary bladder cancer. Scand J Urol Nephrol 2008;42(suppl):12-20.
2.
McKiernan JM, Masson P, Murphy AM, Goetzl IM, Olsson CA, Petrylak DP, Desai M, Benson MC: Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy. J Clin Oncol 2006;24:3075-3080.
3.
Adams JC: Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 2004;16:590-596.
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.
5.
Anilkumar N, Parsons M, Monk R, Ng T, Adams JC: Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility. EMBO J 2003;22:5390-5402.
6.
Hwang JH, Smith CA, Salhia B, Rutka JT: The role of fascin in the migration and invasiveness of malignant glioma cells. Neoplasia 2008;10:149-159.
7.
Karasavvidou F, Barbanis S, Pappa D, Moutzouris G, Tzortzis V, Melekos MD, Koukoulis G: Fascin determination in urothelial carcinomas of the urinary bladder: a marker of invasiveness. Arch Pathol Lab Med 2008;132:1912-1915.
8.
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.
9.
Chiyomaru T, Enokida H, Tatarano S, Kawahara K, Uchida Y, Nishiyama K, Fujimura L, Kikkawa N, Seki N, Nakagawa M: miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer. Br J Cancer 2010;102:883-891.
10.
Soukup V, Babjuk M, Dusková J, Pesl M, Szakáczová M, Zámecník L, Dvorácek J: Does the expression of fascin-1 and tumor subclassification help to assess the risk of recurrence and progression in t1 urothelial urinary bladder carcinoma? Urol Int 2008;80:413-418.
11.
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplexes of 21-nucleotide RNAi-mediate RNA interference in cultured mammalian cells. Nature 2001;411:494-498.
12.
Inoue R, Matsuyama H, Yano S, Yamamoto Y, Iizuka N, Naito K: Gefitinib-related gene signature in bladder cancer cells identified by a cDNA microarray. Anticancer Res 2006;26:4195-4202.
13.
Jawhari AU, BudaA, 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.
14.
Tsai WC, Sheu LF, Nieh S, Yu CP, Sun GH, Lin YF, Chen A, Jin JS: Association of EMMPRIN and fascin expression in renal cell carcinoma: correlation with clinicopathological parameters. World J Urol 2007;25:73-80.
15.
Ozerhan IH, Ersoz N, Onguru O, Ozturk M, Kurt B, Cetiner S: Fascin expression in colorectal carcinomas. Clinics (Sao Paulo) 2010;65:157-164.
16.
Hashimoto Y, Parsons M, Adams JC: Dual actin-bundling and protein kinase C-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. Mol Biol Cell 2007;18:4591-4602.
17.
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.
18.
Fu H, Hu Z, Wen J, Wang K, Liu Y: TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways. Acta Biochim Biophys Sin 2009;41:648-656.
19.
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.
20.
Hashimoto Y, Loftis DW, Adams JC: Fascin-1 promoter activity is regulated by CREB and the aryl hydrocarbon receptor in human carcinoma cells. PLoS One 2009;4:e5130.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.