Published online 1 May 2006. doi:10.1083/jcb.200510115
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 3, 395-404
The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors
Weigang Wang1,
Ghassan Mouneimne1,
Mazen Sidani1,
Jeffrey Wyckoff1,
Xiaoming Chen1,
Anastasia Makris2,
Sumanta Goswami1,
Anne R. Bresnick2, and
John S. Condeelis1
1 Department of Anatomy and Structural Biology and 2 Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461
Correspondence to Weigang Wang: wgwang{at}aecom.yu.edu
Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serinethreonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:11191128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:3686836875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:72477252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.
W. Wang and G. Mouneimne contributed equally to this paper.
Abbreviation used in this paper: LIMK, LIM kinase.

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