Inhibition of invasiveness of human lung cancer cell line H1299 by over-expression of cofilin

Cell Biol Int. 2005 Nov;29(11):877-83. doi: 10.1016/j.cellbi.2005.07.005.

Abstract

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 p27(kip1), which is known to be involved in regulating cell motility. Removal of cofilin over-expression normalizes the p27(kip1) level and concomitantly restores the invasiveness of the cultured cells. These findings suggest that excessive cofilin production might prevent cancer cell invasion.

MeSH terms

  • Actins / chemistry
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Cofilin 1 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Doxycycline / pharmacology
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Microscopy, Fluorescence
  • Neoplasm Invasiveness
  • Plasmids / metabolism
  • Time Factors
  • Transfection
  • Ubiquitin / chemistry

Substances

  • Actins
  • Cofilin 1
  • Ubiquitin
  • Cyclin-Dependent Kinase Inhibitor p27
  • Doxycycline