Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins

Cell. 1994 May 20;77(4):537-49. doi: 10.1016/0092-8674(94)90216-x.


Using proviral tagging in combination with in vitro selection for invasiveness, we have identified a gene, designated Tiam-1, that affects invasion. In the selected invasive T lymphoma variants, proviral insertions were found within coding exons of the Tiam-1 gene, resulting in both truncated 5'-end and 3'-end transcripts that give rise to N- and C-terminal Tiam-1 protein fragments. In one invasive variant, amplification of the Tiam-1 locus was observed with concomitant increase in the amount of normal Tiam-1 protein. Cell clones that were invasive in vitro produced experimental metastases in nude mice, and transfection of truncated Tiam-1 cDNAs into noninvasive cells made these cells invasive. The predicted Tiam-1 protein harbors a Dbl- and Pleckstrin-homologous domain, which it shares with GDP-GTP exchangers for Rho-like proteins that have been implicated in cytoskeletal organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA, Complementary / analysis
  • DNA, Neoplasm / analysis
  • Fungal Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Guanine Nucleotide Exchange Factors
  • Lymphatic Metastasis
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / microbiology
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Moloney murine leukemia virus / genetics
  • Mutagenesis, Insertional
  • Neoplasm Invasiveness / genetics*
  • Oncogene Proteins / genetics
  • Proteins / chemistry
  • Proteins / genetics*
  • Proto-Oncogene Proteins / genetics
  • Restriction Mapping
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tumor Cells, Cultured
  • Virus Integration / genetics
  • rap GTP-Binding Proteins


  • DNA, Complementary
  • DNA, Neoplasm
  • Fungal Proteins
  • Guanine Nucleotide Exchange Factors
  • Oncogene Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • Tiam1 protein, mouse
  • GTP-Binding Proteins
  • rap GTP-Binding Proteins

Associated data

  • GENBANK/U05245