Inhibition of invasiveness of human lung cancer cell line H1299 by over-expression of cofilin.
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.
Lee
Yi-Jang
YJ
Department of Therapeutic Radiology, Yale University, 333 Cedar Street, New Haven, CT 06510, USA. y1343@e-mail.med.yale.edu
Mazzatti
Dawn J
DJ
Yun
Zhong
Z
Keng
Peter C
PC
D000199:Actins / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D051338:Cofilin 1 / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000737:chemistry
D000199:Actins; D051338:Cofilin 1; D025801:Ubiquitin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004318:Doxycycline