|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (2005) 29, 877883 (Printed in Great Britain)
Inhibition of invasiveness of human lung cancer cell line H1299 by over-expression of cofilin
Yi‑Jang Leea*, Dawn J. Mazzattib, Zhong Yuna and Peter C. Kengb
aDepartment of Therapeutic Radiology, Yale University, 333 Cedar Street, New Haven, CT 06510, USA
bCancer Center, University of Rochester, Rochester, NY 14627, USA
The Rho–LIM-kinase (LIMK) signaling pathway, believed to be involved in the regulation of tumor invasion, specifically regulates the activity of cofilin. However, it is unclear whether cofilin plays a pivotal role in tumor invasiveness. In this paper we show using a tet-on gene expression system that over-expression of cofilin inhibits the invasiveness of human lung cancer H1299 cells. Over-expressed cofilin disrupts the actin cytoskeleton at the leading edge of the cell and up-regulates p27kip1, which is known to be involved in regulating cell motility. Removal of cofilin over-expression normalizes the p27kip1 level and concomitantly restores the invasiveness of the cultured cells. These findings suggest that excessive cofilin production might prevent cancer cell invasion.
Key words: Cofilin, Cancer cell invasion, Actin cytoskeleton, p27kip1.
*Corresponding author. Fax: +1 860 632 7734.
Received 24 December 2004/7 July 2005; accepted 13 July 2005doi:10.1016/j.cellbi.2005.07.005