Regulation of tumor invasion and metastasis in protein kinase C epsilon-transformed NIH3T3 fibroblasts

✍ Scribed by Souvenir D. Tachado; Mark W. Mayhew; Ginger G. Wescott; Tonia L. Foreman; Crystal D. Goodwin; Meagan A. McJilton; David M. Terrian

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 264 KB
• Volume: 85
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10164

✦ Synopsis

Abstract

Protein kinase C epsilon is an oncogenic, actin nucleating protein that coordinately regulates changes in cell growth and shape. Cells constitutively expressing PKCϵ spontaneously acquire a polarized morphology and extend long cellular membrane protrusions. Here we report that the regulatory C1 domain of PKCϵ contains an actin binding site that is essential for the formation of elongate invadopodial‐like structures, increased pericellular metalloproteinase activity, in vitro invasion of a Matrigel barrier, and the invasion and metastasis of tumors grown in vivo by PKCϵ‐transformed NIH3T3 fibroblasts in nude mice. While removing this small actin binding motif caused a dramatic reversion of tumor invasion, the deletion mutant of PKCϵ remained oncogenic and tumorigenic in this experimental system. We propose that PKCϵ directly interacts with actin to stimulate polymerization and the extension of membrane protrusions that transformed NIH3T3 cells use in vivo to penetrate and degrade surrounding tissue boundaries. J. Cell. Biochem. 85: 785–797, 2002. © 2002 Wiley‐Liss, Inc.