Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins.
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.
Habets
G G
GG
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam.
Scholtes
E H
EH
Zuydgeest
D
D
van der Kammen
R A
RA
Stam
J C
JC
Berns
A
A
Collard
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D008207:Lymphatic Metastasis; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D016254:Mutagenesis, Insertional; D009361:Neoplasm Invasiveness / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014407:Tumor Cells, Cultured; D016662:Virus Integration / Q000235:genetics; D020668:rap GTP-Binding Proteins
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins