Advertisement

Gelsolin‐induced epithelial cell invasion is dependent on Ras–Rac signaling

Veerle De Corte, Erik Bruyneel, Ciska Boucherie, Marc Mareel, Joël Vandekerckhove, Jan Gettemans

Author Affiliations

  1. Veerle De Corte1,
  2. Erik Bruyneel2,
  3. Ciska Boucherie1,
  4. Marc Mareel2,
  5. Joël Vandekerckhove1 and
  6. Jan Gettemans*,1
  1. 1 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
  2. 2 Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital (1P7), De Pintelaan 185, B‐9000, Ghent, Belgium
  1. *Corresponding author. E-mail: jan.gettemans{at}rug.ac.be
View Full Text

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 1α 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.

  • Received August 8, 2002.
  • Revision received October 25, 2002.
  • Accepted October 29, 2002.
View Full Text