AP-1 differentially expressed proteins Krp1 and fibronectin cooperatively enhance Rho-ROCK-independent mesenchymal invasion by altering the function, localization, and activity of nondifferentially expressed proteins

Heather J Spence, Lynn McGarry, Catherine S Chew, Neil O Carragher, Linda A Scott-Carragher, Zhengqiang Yuan, Daniel R Croft, Michael F Olson, Margaret Frame, Bradford W Ozanne

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor AP-1, which is composed of Fos and Jun family proteins, plays an essential role in tumor cell invasion by altering gene expression. We report here that Krp1, the AP-1 up-regulated protein that has a role in pseudopodial elongation in v-Fos-transformed rat fibroblast cells, forms a novel interaction with the nondifferentially expressed actin binding protein Lasp-1. Krp1 and Lasp-1 colocalize with actin at the tips of pseudopodia, and this localization is maintained by continued AP-1 mediated down-regulation of fibronectin that in turn suppresses integrin and Rho-ROCK signaling and allows pseudopodial protrusion and mesenchyme-like invasion. Mutation analysis of Lasp-1 demonstrates that its SH3 domain is necessary for pseudopodial extension and invasion. The results support the concept of an AP-1-regulated multigenic invasion program in which proteins encoded by differentially expressed genes direct the function, localization, and activity of proteins that are not differentially expressed to enhance the invasiveness of cells.
Original languageEnglish
Pages (from-to)1480-95
Number of pages16
JournalMolecular and Cellular Biology
Volume26
Issue number4
DOIs
Publication statusPublished - Feb 2006

Keywords

  • Animals
  • Carrier Proteins
  • Cell Line
  • Cell Transformation, Neoplastic
  • Fibronectins
  • Genes, fos
  • Intracellular Signaling Peptides and Proteins
  • Mesoderm
  • Microfilament Proteins
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Neoplasm Invasiveness
  • Nerve Tissue Proteins
  • Phenotype
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Pseudopodia
  • RNA, Small Interfering
  • Rats
  • Signal Transduction
  • Transcription Factor AP-1
  • rho-Associated Kinases

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