Article
- The EMBO Journal (2002) 21, 6781 - 6790
- doi:10.1093/emboj/cdf680
Subject Categories:
Gelsolin-induced epithelial cell invasion is dependent on Ras–Rac signaling
Veerle De Corte1, Erik Bruyneel2, Ciska Boucherie1, Marc Mareel2, Joël Vandekerckhove1 and Jan Gettemans1
- Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Rommelaere Institute, Albert Baertsoenkaai 3, B-9000 Gent, Belgium and Flanders Interuniversity Institute for Biotechnology (V.I.B.), De Pintelaan 185, B-9000 Ghent, Belgium
- Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital (1P7), De Pintelaan 185, B-9000 Ghent, Belgium
Correspondence to:
Jan Gettemans, E-mail: jan.gettemans@rug.ac.be
Received 8 August 2002; Accepted 29 October 2002; Revised 25 October 2002
Abstract
Gelsolin is a widely distributed actin binding protein involved in controlling cell morphology, motility, signaling and apoptosis. The role of gelsolin in tumor progression, however, remains poorly understood. Here we show that expression of green fluorescent pro tein (GFP)-tagged gelsolin in MDCK-AZ, MDCKtsSrc or HEK293T cells promotes invasion into collagen type I. In organ culture assays, MDCK cells expressing gelsolin–GFP invaded pre-cultured chick heart fragments. Gelsolin expression inhibited E-cadherin-mediated cell aggregation but did not disrupt the E-cadherin–catenin complex. Co-expression of dominant-negative Rac1N17, but not RhoAN19 or Cdc42N17, counteracted gelsolin-induced invasion, suggesting a requirement for Rac1 activity. Increased ARF6, PLD or PIP5K 1
activity canceled out gelsolin-induced invasion. Furthermore, we found that invasion induced by gelsolin is dependent on Ras activity, acting through the PI3K–Rac pathway via the Ras guanine nucleotide exchange factor Sos-1. These findings establish a connection between gelsolin and the Ras oncogenic signaling pathway.
Keywords:
- actin binding protein,
- collagen invasion,
- gelsolin,
- Ras signaling
