Molecular Biology of the Cell Call for Nominations: MBC Editor-in-Chief

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E07-02-0157 on September 12, 2007

Vol. 18, Issue 11, 4591-4602, November 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-02-0157v1
18/11/4591    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hashimoto, Y.
Right arrow Articles by Adams, J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hashimoto, Y.
Right arrow Articles by Adams, J. C.

Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to MetastasisFormula Formula

Yosuke Hashimoto*, Maddy Parsons{dagger}, and Josephine C. Adams*,{ddagger}

*Department of Cell Biology, Lerner Research Institute, and {ddagger}Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, The Cleveland Clinic, Cleveland, OH 44195; and {dagger}Randall Division of Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, United Kingdom

Submitted February 21, 2007; Revised August 29, 2007; Accepted August 31, 2007
Monitoring Editor: Yu-li Wang

Recurrence of carcinomas due to cells that migrate away from the primary tumor is a major problem in cancer treatment. Immunohistochemical analyses of human carcinomas have consistently correlated up-regulation of the actin-bundling protein fascin with a clinically aggressive phenotype and poor prognosis. To understand the functional and mechanistic contributions of fascin, we undertook inducible short hairpin RNA (shRNA) knockdown of fascin in human colon carcinoma cells derived from an aggressive primary tumor. Fascin-depletion led to decreased numbers of filopodia and altered morphology of cell protrusions, decreased Rac-dependent migration on laminin, decreased turnover of focal adhesions, and, in vivo, decreased xenograft tumor development and metastasis. cDNA rescue of fascin shRNA-knockdown cells with wild-type green fluorescent protein-fascin or fascins mutated at the protein kinase C (PKC) phosphorylation site revealed that both the actin-bundling and active PKC-binding activities of fascin are required for the organization of filopodial protrusions, Rac-dependent migration, and tumor metastasis. Thus, fascin contributes to carcinoma migration and metastasis through dual pathways that impact on multiple subcellular structures needed for cell migration.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-02-0157) on September 12, 2007.

Formula Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Josephine C. Adams (adamsj{at}ccf.org)

Abbreviations used: BIM, bisindolylmaleimide I; IKD, inducible knockdown; LN, laminin; mRFP, monomer red fluorescent protein; shRNA, short hairpin RNA; TetR, tetracycline repressor.






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.