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

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


     

MBC in Press, published online ahead of print September 12, 2007
Mol. Biol. Cell 10.1091/mbc.E07-02-0157

A more recent version of this article appeared on November 1, 2007
This Article
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 HighWire
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.

Submitted on February 21, 2007
Revised on August 29, 2007
Accepted on August 31, 2007

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

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; {dagger}Randall Division of Cell and Molecular Biophysics, King’s College London, Guy’s Campus, London SE1 1UL, United Kingdom

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 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 GFP-fascin or fascins mutated at the 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.

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




This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
M. Parsons and J. C. Adams
Rac regulates the interaction of fascin with protein kinase C in cell migration
J. Cell Sci., September 1, 2008; 121(17): 2805 - 2813.
[Abstract] [Full Text] [PDF]


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