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Role of Tiam 1 in Rac-Mediated Signal Transduction Pathways

  • J. G. Collard
  • G. G. M. Habets
  • F. Michiels
  • J. Stam
  • R. A. van der Kammen
  • F. van Leeuwen
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 213/2)

Abstract

Metastasis is a multistep process that requires the complex interplay of a number of gene products. Many tumour cell properties have been correlated with metastatic capacity, but direct evidence for a role of specific genes in metastasis is scarce. Products of oncogenes, such as Ras, can confer metastatic capacity (see Collard et al. 1988), as can specific splice variants of CD44, of which the expression correlates with metastasis in model systems and certain human tumours (Günthert et al. 1991; Wielenga et al. 1993). In contrast, other gene products such as Nm23, which shows homology to nucleoside diphosphate kinases, can supress metastasis (Leone et al. 1991), and downmodulation of Nm23 in mammary carcinomas has been associated with poor prognosis (Bevilacqua et al. 1989). Proteins involved in invasion also influence metastasis, as has been shown for proteases and their inhibitors (Liotta et al. 1991) and for adhesion molecules that play a role in cell-cell and cell-matrix interactions, e.g. E-cadherin (Behrens et al. 1990; Vleminckx et al. 1991) and certain integrins (Roosein et al. 1989; Chan et al. 1991). In order to identify genes specifically involved in the acquisition of the invasive and metastatic phenotype of tumorigenic cells, we have used proviral tagging in combination with in vitro selection for invasive T lymphoma cells. These studies have led to the identification of the Tiam 1 gene, which encodes a protein that regulates the activation of Racmediated signalling pathways.

Keywords

NIH3T3 Cell Membrane Ruffling Oncogenic Phenotype Guanine Nucleotide Dissociation Inhibitor Invasive Variant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Arcaro A, Wymann MP (1993) Worthmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3, 4, 5-triphosphate in neutrophil responses. Biochem J 296: 297–301PubMedGoogle Scholar
  2. Avraham H, Weinberg RA (1989) Characterization and expression of the human rho 12 gene product. Mol Cell Biol 9: 2058–2066PubMedGoogle Scholar
  3. Behrens J, Mareel MM, Van Roy FM, Birchmeier W (1990) Dissecting tumor cell invasion: epithelial cells acquire invasive properties after loss of Uvomorulin-mediated cell-cell adhesion. J Cell Biol 108: 2435–2447CrossRefGoogle Scholar
  4. Bevilacqua G, Sobel ME, Liotta LA, Steeg PS (1989) Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res 49: 5185–5190PubMedGoogle Scholar
  5. Boguski MS, McCormick F (1993) Proteins regulating Ras and its relatives. Nature 366: 643–654PubMedCrossRefGoogle Scholar
  6. Bourne HR, Sanders DA, McCormick F (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348: 125–132PubMedCrossRefGoogle Scholar
  7. Bourne HR, Sanders DA, McCormick F (1991) The GTPase superfamily: conserved structure and molecular mechanism. Nature 349: 117–127PubMedCrossRefGoogle Scholar
  8. Buday L, Downward J (1993) Epidermal growth factor regulates p21(ras) through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor. Cell 73: 611–620PubMedCrossRefGoogle Scholar
  9. Chan BMC, Matsuura N, Takada Y, Zetter BR, Hemler ME (1991) In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science 251: 1600–1602PubMedCrossRefGoogle Scholar
  10. Chardin P, Boquet P, Madaule P, Popoff MR, Rubin EJ, Gill DM (1989) The mammalian G protein rho C is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in vero cells. EMBO J 8: 1087–1092PubMedGoogle Scholar
  11. Chong LD, Traynorkaplan A, Bokoch GM, Schwartz MA (1994) The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells. Cell 79: 507–513PubMedCrossRefGoogle Scholar
  12. Collard JG, Schijven JF, Roos E (1987a) Invasive and metastatic potential induced by ras-transfection into mouse BW5147 T lymphoma cells. Cancer Res 47: 754–759PubMedGoogle Scholar
  13. Collard JG, Van de Poll M, Scheffer A, Roos E, Hopman AHM, Geurts van Kessel AHM, Van Dongen JJM (1987b) Location of genes involved in invasion and metastasis on human chromosome 7. Cancer Res 47: 6666–6670PubMedGoogle Scholar
  14. Collard JG, Roos E, La Rivière G, Habets GGM (1988) Genetic analysis of invasion and metastasis. Cancer Surv 7: 692–710Google Scholar
  15. Collard JG, Habets GGM, Van der Kammen R, Scholtes E (1989) Genetic basis of T lymphoma invasion. Invasion Metastasis 9: 379–390PubMedGoogle Scholar
  16. Cook S, McCormick F (1994) Signal transduction-Ras blooms on sterile ground. Nature 369: 361–362PubMedCrossRefGoogle Scholar
  17. Downward J (1992) Signal transduction. Rae and Rho in tune. Nature 359: 273–274PubMedCrossRefGoogle Scholar
  18. Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM (1993) Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation. Nature 363: 45–51PubMedCrossRefGoogle Scholar
  19. Eva A, Vecchio G, Rao CD, Tronick SR, Aaronson SA (1988) The predicted DBL oncogene product defines a distinct class of transforming proteins. Proc Natl Acad Sci USA 85: 2061–2065PubMedCrossRefGoogle Scholar
  20. Fry MJ, Waterfield MD (1993) Structure and function of phosphatidylinositol 3-kinase: a potential second messenger system involved in growth control. Philos Trans R Soc Lond Biol 340: 337–344PubMedCrossRefGoogle Scholar
  21. Fukami K, Furuhashi K, Inagaki M, Endo T, Hatano S, Takenawa T (1992) Requirement of phosphatidylinositol 4, 5-bisphosphate for alpha-actinin function. Nature 359: 150–152PubMedCrossRefGoogle Scholar
  22. Gale NW, Kaplan S, Lowenstein EJ, Schlessinger J, Barsagi D (1993) Grb2 Mediates the EGF-dependent activation of guanine nucleotide Exchange on Ras. Nature 363: 88–92PubMedCrossRefGoogle Scholar
  23. Gibson TJ, Hyvonen M, Birney E, Musacchio A, Saraste M (1994) PH domain-the first anniversary. Trends Biochem Sci 19: 349–353PubMedCrossRefGoogle Scholar
  24. Günthert U, Hofmann M, Rudy W, Reber S, Zöller M, Haussman I, Matzku S, Wenzel A, Ponta H, Herrlich P (1991) A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65: 13–24PubMedCrossRefGoogle Scholar
  25. Habets GGM, Van der Kammen R, Scholtes WHM, Collard JG (1990) Induction of invasive and metastatic potential in mouse T lymphoma cells (BW5147) by treatment with 5-azacytidine. Clin Exp Metastasis 8: 567–577PubMedCrossRefGoogle Scholar
  26. Habets GGM, Van der Kammen RA, Willemsen V, Balemans M, Wiegant J, Collard JG (1992) Sublocalization of an invasion-inducing locus and other genes on human chromosome 7. Cytogenet Cell Genet 60: 200–205PubMedCrossRefGoogle Scholar
  27. Habets GGM, Scholtes EHM, Zuydgeest D, Van der Kammen RA, Stam JC, Berns A, Collard JG (1994) Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for rho-like proteins. Cell 77: 537–549PubMedCrossRefGoogle Scholar
  28. Habets GGM, Van der Kammen RA, Jenkins NA, Gilbert DJ, Copeland NG, Hagemeijer A, Collard JG (1995a) The invasion-inducing TIAM-1 gene maps to human chromosome band 21q22 and mouse chromosome 16. Cytogenet Cell Genet 70: 48–51PubMedCrossRefGoogle Scholar
  29. Habets GGM, van der Kammen RA, Stam JC, Michiels F, Collard JG (1995b) Sequence of the human invasion-inducing TIAM1 gene, its conversion in evolution and its expression in tumor cell lines of different tissue origin. Oncogene 10: 1371–1376PubMedGoogle Scholar
  30. Hall A (1990) The cellular functions of small GTP-binding proteins. Science 249: 635–640PubMedCrossRefGoogle Scholar
  31. Hall A (1992) Ras-related GTPases and the cytoskeleton. Mol Biol Cell 3: 475–479PubMedGoogle Scholar
  32. Harlan JE, Hajduk PJ, Yoon HS, Fesik SW (1994) Pleckstrin homology domains bind to phosphatidylinositol-4, 5-bisphosphate. Nature 371: 168–170PubMedCrossRefGoogle Scholar
  33. Hart MJ, Eva A, Zangrilli D, Aaronson SA, Evans T, Cerione RA, Zheng Y (1994) Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product. J Biol Chem 269: 62–65PubMedGoogle Scholar
  34. Horii Y, Beeler JF, Sakaguchi K, Tachibana M, Miki T (1994) A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentiality links Rho and Rae signaling pathways. EMBO J 13: 4776–4786PubMedGoogle Scholar
  35. Imamura F, Horai T, Mukai M, Shinkai K, Sawada M, Akedo H (1993) Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D. Biochem Biophys Res Commun 193: 497–503PubMedCrossRefGoogle Scholar
  36. Katzav S, Martin-Zanca D, Barbacid M (1989) Vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J 8: 2283–2290PubMedGoogle Scholar
  37. Katzav S, Cleveland JL, Heslop HE, Pulido D (1991) Loss of the amino-terminal helix-loop-helix domain of the vav proto-oncogene activates its transforming potential. Mol Cell Biol 11: 1912–1920PubMedGoogle Scholar
  38. Lassing I, Lindberg U (1985) Specific interaction between phosphatidylinositol 4, 5 bisphosphate and profilactin. Nature 314: 472–474CrossRefGoogle Scholar
  39. Leevers SJ, Paterson HF, Marshall CJ (1994) Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature 369: 411–420PubMedCrossRefGoogle Scholar
  40. Leone A, Flatow U, King CR, Sandeen MA, Margulies IM, Liotta LA, Steeg PS (1991) Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 65: 25–35PubMedCrossRefGoogle Scholar
  41. Liotta LA, Steeg P, Stetler Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336PubMedCrossRefGoogle Scholar
  42. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L (1994) A brain serine threonine protein kinase activated by Cdc42 and Rac1. Nature 367: 40–46PubMedCrossRefGoogle Scholar
  43. McGlade J, Brunkhorst B, Anderson D, Mbamalu G, Settleman J, Dedhar S, Rozakis-Adcock M, Chen LB, Pawson T (1993) The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. EMBO J 12: 3073–3081PubMedGoogle Scholar
  44. Michiels F, Habets GGM, Stam JC, Van der Kammen RA, Collard JG (1995) A role for Rae in Tiaml-induced membrane ruffling and invasion. Nature 375: 338–340PubMedCrossRefGoogle Scholar
  45. Miki T, Smith CL, Long JE, Eva A, Fleming TP (1993) Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature 362: 462–465 (erratum published in Nature 364: 737)Google Scholar
  46. Nobes C, Hawkins P, Stephens L, Hall A (1995) Activation of the small GTP-binding proteins Rho and Rae by growth factor receptors. J Cell Sci 108: 225–233PubMedGoogle Scholar
  47. Parker PJ, Waterfield MD (1992) Phosphatidylinositol 3-kinase: a novel effector. Cell Growth Differ 3: 747–752PubMedGoogle Scholar
  48. Paterson HF, Self AJ, Garrett MD, Just I, Aktories K, Hall A (1990) Microinjection of recombinant p21 rho induces rapid changes in cell morphology. J Cell Biol 111: 1001–1007PubMedCrossRefGoogle Scholar
  49. Perona R, Esteve P, Jimenez B, Ballestero RP, Cajal SR (1993) Tumorigenic activity of rho genes from aplysia-californica. Oncogene 8: 1285–1292PubMedGoogle Scholar
  50. Ponting CP, Philips C (1995) DHR domains in synthrophins, neuronal NO synthases and other intracellular proteins. Trends Biochem Sci 20: 102–103PubMedCrossRefGoogle Scholar
  51. Qiu R, Kirn D, McCormick F, Symons M (1995) An essential role for Rae in Ras transformation. Nature 374: 457–459PubMedCrossRefGoogle Scholar
  52. Reinhard J, Scheel AA, Diekmann D, Hall A, Ruppert C, Bahler M (1995) A novel type of myosin implicated in signalling by Rho family GTPases. EMBO J 14: 101–108Google Scholar
  53. Ridley AJ (1994) Membrane ruffling and signal transduction. Bioessays 16: 321–327PubMedCrossRefGoogle Scholar
  54. Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibres in response to growth factors. Cell 70: 389–399PubMedCrossRefGoogle Scholar
  55. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70: 401–410PubMedCrossRefGoogle Scholar
  56. Ridley A, Self AJ, Kasmi F, Paterson HF, Hall A, Marshall CJ, Ellis C (1993) Rho family GTPase activating proteins p190, Ber and RhoGAP show distinct specificities in vitro and in vivo. EMBO J 12: 5151–5160PubMedGoogle Scholar
  57. Roos E, La Rivière G, Collard JG, Stukart MJ, de Baetselier P (1985) Invasiveness of T cell hybridomas in vitro and their metastatic potential in vivo. Cancer Res 45: 6238–6243PubMedGoogle Scholar
  58. Roossien FF, de Rijk D, Bikker A, Roos E (1989) Involvement of LFA-1 in lymphoma invasion and metastasis demonstrated with LFA-1-deficient mutants. J Cell Biol 108: 1979–1985PubMedCrossRefGoogle Scholar
  59. Sekine A, Fujiwara M, Narumiya S (1989) Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase. J Biol Chem 264: 8602–8605PubMedGoogle Scholar
  60. Settleman J, Albright CF, Foster LC, Weinberg RA (1992a) Association between GTPase activators for Rho and Ras families. Nature 359: 153–154PubMedCrossRefGoogle Scholar
  61. Settleman J, Narashimhan V, Foster LC, Weinberg RA (1992b) Molecular cloning of cdnas encoding the gap-associated protein p190: implications for a signaling pathway from ras to the nucleus. Cell 69: 539–549PubMedCrossRefGoogle Scholar
  62. Simon MA, Dodson GS, Rubin GM (1993) An SH3-SH2-SH3 protein is required for p21 (Ras1) activation and binds to sevenless and Sos proteins in vitro. Cell 73: 169–177PubMedCrossRefGoogle Scholar
  63. Takaishi K, Kikuchi A, Kuroda S, Kotani K, Sasaki T, Takai Y (1993) Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility. Mol Cell Biol 13: 72–79PubMedGoogle Scholar
  64. Takaishi K, Sasaski T, Kato M, Yamochi W, Kuroda S, Nakamura T, Takeichi M, Takai Y (1994) involvement of Rho P21 small GTP-binding protein and its regulator in the HGF-induced cell motility. Oncogene 9: 273–279PubMedGoogle Scholar
  65. Tominaga T, Sugie K, Hirata M, Morii N, Fukata J, Uchida A, Narumiya S (1993) Inhibition of PMA-induced, lfa-1 -dependent lymphocyte aggregation by ADP ribosylation of the small molecular weight GTP binding protein, rho. J Cell Biol 120: 1529–1537PubMedCrossRefGoogle Scholar
  66. van Corven EJ, Groenink A, Jalink K, Eichholtz T, Moolenaar WH (1989) Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell 59: 45–54PubMedCrossRefGoogle Scholar
  67. van der Bend RL, Brunner J, Jalink K, van Corven EJ, Moolenaar WH, van Blitters WJ (1992) Identification of a putative membrane receptor for the bioactive phospholipid, lysophosphatidic acid. EMBO J 11: 2495–2501PubMedGoogle Scholar
  68. van Leeuwen FN, van der Kammen RA, Habets GGM, Collard JG (1995) Oncogenic activity of Tiaml and Rac1 in NIH3T3 cells. Oncogene 11: 2215–2221PubMedGoogle Scholar
  69. Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, Van Roy F (1991) Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66: 107–119PubMedCrossRefGoogle Scholar
  70. Wennstrom S, Hawkins P, Cooke F, Hara K, Yonezawa K, Kasuga M, Jackson T, Claesson-Welsh L, Stephens L (1994) Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling. Curr Biol 4: 385–393PubMedCrossRefGoogle Scholar
  71. Weilenga VJM, Heider KH, Offerhaus GJA, Adolf GR, Van Den berg FM, Ponta H, Herrlich P, Pals ST (1993) Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res 53: 4754–4756Google Scholar
  72. Yano H, Nakanishi S, Kimura K, Hanai N, Saitoh Y, Fukui Y, Nonomura Y, Matsuda Y (1993) Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL- 2H3 cells. J Biol Chem 268: 25846–25856PubMedGoogle Scholar
  73. Zheng Y, Cerione R, Bender A (1994) Control of the yeast bud-site assembly GTPase Cdc42 — catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3. J Biol Chem 269: 2369–2372PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • J. G. Collard
    • 1
  • G. G. M. Habets
    • 1
  • F. Michiels
    • 1
  • J. Stam
    • 1
  • R. A. van der Kammen
    • 1
  • F. van Leeuwen
    • 1
  1. 1.Division of Cell BiologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands

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