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Published online November 19, 2007
doi:10.1083/jcb.200707009
The Journal of Cell Biology, Vol. 179, No. 4, 777-791
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Sidani et al.
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Article

 Cofilin determines the migration behavior and turning frequency of metastatic cancer cells

Mazen Sidani1, Deborah Wessels5, Ghassan Mouneimne1, Mousumi Ghosh1, Sumanta Goswami1,4, Corina Sarmiento1, Weigang Wang1, Spencer Kuhl5, Mirvat El-Sibai2, Jonathan M. Backer2, Robert Eddy1, David Soll5, and John Condeelis1,3

1 Department of Anatomy and Structural Biology, 2 Department of Molecular Pharmacology, 3 Gruss-Lipper Biophotonics Center, and 4 Department of Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461
5 W.M. Keck Dynamic Image Analysis Facility, Department of Biological Sciences, The University of Iowa, Iowa City, IA 52242

Correspondence to Mazen Sidani: msidani{at}aecom.yu.edu

We have investigated the effects of inhibiting the expression of cofilin to understand its role in protrusion dynamics in metastatic tumor cells, in particular. We show that the suppression of cofilin expression in MTLn3 cells (an apolar randomly moving amoeboid metastatic tumor cell) caused them to extend protrusions from only one pole, elongate, and move rectilinearly. This remarkable transformation was correlated with slower extension of fewer, more stable lamellipodia leading to a reduced turning frequency. Hence, the loss of cofilin caused an amoeboid tumor cell to assume a mesenchymal-type mode of movement. These phenotypes were correlated with the loss of uniform chemotactic sensitivity of the cell surface to EGF stimulation, demonstrating that to chemotax efficiently, a cell must be able to respond to chemotactic stimulation at any region on its surface. The changes in cell shape, directional migration, and turning frequency were related to the re-localization of Arp2/3 complex to one pole of the cell upon suppression of cofilin expression.

D. Wessels and G. Mouneimne contributed equally to this paper.

Abbreviations used in this paper: Arp2/3 complex, actin-related protein complex; CF KD, cofilin siRNA knockdown; DIAS, dynamic image analysis software; ZBP, zip code binding protein.


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