Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

G-protein αolf subunit promotes cellular invasion, survival, and neuroendocrine differentiation in digestive and urogenital epithelial cells

Oncogene volume 21, pages 4020–4031 (2002)Cite this article

Abstract

The heterotrimeric G-protein subunits Gα and Gβγ are involved in cellular transformation and tumor development. Here, we report the expression of Gαolf in human digestive and urogenital epithelial cells using RT–PCR and Western blot. When the constitutively activated form of GαolfQ214L (AGαolf) was stably transfected in canine kidney MDCKts.src and human colonic HCT-8/S11 epithelial cells, it induced cellular invasion in collagen gels. AGαolf-mediated invasion was abrogated by agonists of platelet activating factor receptors (PAF-R) and protease-activated receptors -1 (PAR-1), pharmacological inhibitors of PI3′-Kinase (wortmannin), protein kinase C (Gö6976 and GF109203X), Rho GTPase (C3T exoenzyme), but was independent of protein kinase A. Accordingly, the invasive phenotype induced by AGαolf in HCT-8/S11 cells was reversed by the RhoA antagonist RhoD (G26V). Although AGαolf protected MDCKts.src cells against serum starvation-mediated apoptosis via a Rho-independent pathway, both AGαolf and Rho inhibition by C3T induced neuroendocrine-like differentiation linked to extensive neurite outgrowth and parathyroid hormone-related protein expression in human prostatic LNCaP-AGαolf cells. Since prostate tumors with a larger neuroendocrine cell population display increased invasiveness, persistent activation of the G-protein αolf may exert convergent adverse effects on cellular invasion and survival in solid tumors during the neoplastic progression towards metastasis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Akhurst RJ, Derynck R . 2001 TRENDS in Cell Biology 11: S44–S51

  • Astesano A, Régnauld K, Ferrand N, Gingras D, Bendayan M, Rosselin G, Emami S . 1999 J. Histochem. Cytochem. 47: 289–302

  • Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M, Wymann MP, Gespach C . 2000 FASEB J. 14: 2329–2338

  • Barbier M, Attoub S, Calvez R, Laffargue M, Jarry A, Mareel M, Altruda F, Gespach C, Wu D, Lu B, Hirsch E, Wymann MP . 2001 Nature 413: 796–

  • Behrens J, Vakaet L, Friis R, Winterhager E, van Roy F, Mareel MM, Birchmeier W . 1993 J. Cell. Biol. 120: 757–766

  • Bolt MJ, Mailloux RJ, Rasenick MM, Wali RK, Skarosi S, Bissonnette M, Brasitus TA, Sitrin MD . 1998 Gastroenterology 115: 1494–1503

  • Bouvet M, Nardin SR, Burton DW, Behling C, Carethers JM, Moossa AR, Deftos LJ . 2001 J. Clin. Endocrinol. Metab. 86: 310–316

  • Carron JA, Fraser WD, Gallagher JA . 1997 Br. J. Cancer 76: 1095–1098

  • Chastre E, Empereur S, Di Gioia Y, el Mahdani N, Mareel M, Vleminckx K, Van Roy F, Bex V, Emami S, Spandidos DA et al . 1993 Gastroenterology 105: 1776–1789

  • Chien J, Wong E, Nikes E, Noble MJ, Pantazis CG, Shah GV . 1999 Oncogene 18: 3376–3382

  • Cox ME, Deeble PD, Lakhani S, Parsons S . 1999 Cancer Res. 59: 3821–3830

  • Dalle S, Ricketts W, Imamura T, Vollenweider P, Olefsky JM . 2001 J. Biol. Chem. 276: 15688–15695

  • Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotho Y, Greenberg ME . 1997 Cell 91: 231–241

  • Debruyne PR, Bruyneel EA, LI X, Zimber A, Gespach C, Mareel MM . 2001 Mutation Res. 481: 359–369

  • de Curtis I . 2001 EMBO Rep. 2: 277–281

  • Deftos LJ . 2000 Cancer 88: 3002–3008

  • del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G . 1997 Science 278: 687–689

  • de Rooij J, Rehmann H, van Triest M, Cool RH, Wittinghofer A, Bos JL . 2000 J. Biol. Chem. 275: 20829–20836

  • Di Renzo MF, Olivero M, Giacomini A, Porte H, Chastre E, Mirossay L, Nordlinger B, Bretti S, Bottardi S, Giordano S, Plebani M, Gespach C, Comoglio PM . 1995 Clin. Cancer Res. 1: 147–154

  • Du Villard JA, Wicker R, Crespo P, Russo D, Filetti S, Gutkind JS, Sarasin A, Suarez HG . 2000 Oncogene 19: 4896–4905

  • Emami S, Le Floch N, Bruyneel E, Thim L, May F, Westley B, Rio MC, Mareel M, Gespach C . 2001 FASEB J. 15: 351–361

  • Empereur S, Djelloul S, Di Gioia Y, Bruyneel E, Mareel M, Van Hengel J, Van Roy F, Comoglio P, Courtneidge S, Paraskeva C, Chastre E, Gespach C . 1997 Br. J. Cancer 75: 241–250

  • Escande B, Lindner V, Massfelder T, Helwig JJ, Simeoni U . 2001 Semin. Perinatol. 25: 76–84

  • Faivre S, Régnauld K, Bruyneel E, Nguyen Q-D, Mareel M, Emami S, Gespach C . 2001 Mol. Pharmacol. 60: 363–372

  • Farfel Z, Bourne HR, Iiri T . 1999 N. Engl. J. Med. 340: 1012–1020

  • Fearon ER, Vogelstein B . 1990 Cell 61: 759–767

  • Ferrand N, Pessah M, Frayon S, Marais J, Garel JM . 1999 J. Mol. Cell. Cardiol. 5: 1137–1142

  • Fredriksson JM, Lindquist JM, Bronnikov GE, Nedergaard J . 2000 J. Biol. Chem. 275: 13802–13811

  • Gorczyca W, Gong J, Ardelt B, Traganos F, Darzynkiewicz Z . 1993 Cancer Res. 53: 3186–3192

  • Gratacap MP, Payrastre B, Nieswandt B, Offermanns S . 2001 J. Biol. Chem. 276: 47906–47913

  • Gujral A, Burton DW, Terkeltaub R, Deftos LJ . 2001 Cancer Res. 61: 2282–2288

  • Hoosein NM, Logothetis CJ, Chung LW . 1993 J. Urol. 149: 1209–1213

  • Iiri T, Bell SM, Baranski TJ, Fujita T, Bourne HR . 1999 Proc. Natl. Acad. Sci. USA 96: 499–504

  • Irby R, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ . 1999 Nat. Genet. 21: 187–190

  • Jiang H, Wu D, Simon MI . 1993 FEBS Lett. 330: 319–322

  • Jones DT, Reed RR . 1989 Science 244: 790–795

  • Jung YD, Nakano K, Liu W, Gallick G, Ellis LM . 1999 Cancer Res. 59: 4804–4807

  • Katagiri K, Hattori M, Minato N, Irie SK, Takatsu K, Kinashi T . 2000 Mol. Cell. Biol. 20: 1956–1969

  • Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE, Graybiel AM . 1998 Science 282: 2275–2279

  • Kotelevets L, Noë V, Bruyneel E, Myssiakin E, Chastre E, Mareel M, Gespach C . 1998 J. Biol. Chem. 273: 14138–14145

  • Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sterweis PC . 1998 Science 280: 2109–2111

  • Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB . 1996 Nature 379: 311–319

  • Liu T, DeCostanzo AJ, Liu X, Wang HY, Hallagan S, Moon RT, Malbon CC . 2001 Science 292: 1718–1722

  • Logothetis CJ, Hoosein NM, Hsieh JT . 1994 Semin. Oncol. 21: 620–629

  • Lyons J, Landis CA, Harsh G, Vallar L, Grunewald K, Feichtinger H, Duh QY, Clark OH, Kawasaki E, Bourne HR, McCormick F . 1990 Science 249: 655–659

  • Ma YC, Huang XY . 1998 Proc. Natl. Acad. Sci. USA 95: 12197–12201

  • Machesky LM, Hall A . 1997 J. Cell. Biol. 138: 913–926

  • Marinissen MJ, Chiariello M, Pallante M, Gutkind JS . 1999 Mol. Cell. Biol. 19: 42289–42301

  • Marinissen MJ, Gutkind JS . 2001 Trends Pharmacol. Sci. 22: 368–376

  • Moretti F, Nanni S, Pontecorvi A . 2000 Baillieres Best. Pract. Res. Clin. Endocrinol. Metab. 14: 517–539

  • Nguyen QD, Faivre S, Bruyneel E, Rivat C, Seto M, Endo T, Mareel M, Emami S, Gespach C . 2002 FASEB J. 16: 565–576

  • O'Connor KL, Mercurio AM . 2001 J. Biol. Chem. 276: 47895–47900

  • Pap M, Cooper GM . 1998 J. Biol. Chem. 273: 19929–19932

  • Peri A, Conforti B, Baglioni-Peri S, Luciani P, Cioppi F, Buci L, Corbetta S, Ballare E, Serio M, Spada AJ . 2001 Clin. Endocrinol. Metab. 86: 2111–2117

  • Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, Ullrich A . 1999 Nature 402: 884–888

  • Prie D, Friedlander G, Coureau C, Vandewalle A, Cassingena R, Ronco PM . 1995 Kidney Int. 47: 1310–1318

  • Prunier C, Mazars A, Noe V, Bruyneel E, Mareel M, Gespach C, Atfi A . 1999 J. Biol. Chem. 274: 22919–22922

  • Radhika V, Dhanasekaran N . 2001 Oncogene 26: 1607–1614

  • Reedquist KA, Ross E, Koop EA, Wolthuis RM, Zwartkruis FJ, van Kooyk Y, Salmon M, Buckley CD, Bos JL . 2000 J. Cell. Biol. 148: 1151–1158

  • Régnauld KL, Leteurtre E, Gutkind JS, Gespach CP, Emami S . 2002 Am. J. Physiol. 282: R870–R880

  • Ridley AJ, Hall A . 1994 EMBO J. 13: 2600–2610

  • Rius RA, Mollner S, Pfeuffer T, Loh YP . 1994 Brain Res. 643: 50–58

  • Rodrigues S, Nguyen QD, Faivre S, Bruyneel E, Thim L, Westley B, May F, Flatau G, Mareel M, Gespach C, Emami S . 2001 FASEB J. 15: 1517–1528

  • Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L . 1995 Nat. Genet. 10: 143–150

  • Scheid MP, Woodgett JR . 2001 Nature Reviews 2: 760–768

  • Shah GV, Rayford W, Noble MJ, Austenfeld M, Weigel J, Vamos S, Mebust WK . 1994 Endocrinology 134: 596–602

  • Shankar PP, Wei H, Davee SM, Funk JL . 2000 Brain Res. 868: 230–240

  • Shaw LM . 2001 Mol. Cell. Biol. 21: 5082–5093

  • Spada A, Lania A, Ballare EG . 1998 Mol. Cell. Endocrinol. 14: 1–14

  • Talamonti MS, Roh MS, Curley SA, Gallick GE . 1993 J. Clin. Invest. 91: 53–60

  • Tsai RY, Reed RR . 1997 J. Neurosci. 17: 4159–4169

  • Tsubakimoto K, Matsumoto K, Abe H, Ishii J, Amano M, Kaibuchi K, Endo T . 1999 Oncogene 18: 2431–2440

  • Ueda H, Morishita R, Yamauchi J, Itoh H, Kato K, Asano T . 2001 J. Biol. Chem. 276: 6846–6852

  • Van Leeuwen FN, Kain HE, van der Kamman RA, Michiels F, Kranenburg OW, Collard JG . 1997 J. Cell Biol. 139: 797–807

  • Vara Prasad MV, Dhanasekaran N . 1999 Oncogene 18: 1639–1642

  • Vermeulen SF, Bruyneel EA, Bracke ME, De Bruyne GK, Vennekens KM, Vleminckx KL, Berx GJ, van Roy FM, Mareel MM . 1995 Cancer Res. 55: 4722–4728

  • Vider BZ, Zimber A, Chastre E, Gespach C, Halperin M, Mashiah P, Yaniv A, Gazit A . 2000 Biochem. Biophys. Res. Commun. 272: 513–518

  • Vleminckx K, Vakaet L, Mareel M, Fiers W, van Roy F . 1991 Cell 66: 107–119

  • Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ . 1997 Cell 89: 73–82

  • Wang MM, Tsai RY, Schrader KA, Reed RR . 1993 Mol. Cell. Biol. 13: 5805–5813

  • Xu N, Voyno-Yasenetskaya T, Gutkind JS . 1994 Biochem. Biophys. Res. Commun. 201: 603–609

  • Yao R, Cooper GM . 1995 Science 267: 2003–2006

  • York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW, Stork PJ . 1998 Nature 392: 622–626

  • Young MR, Montpetit M, Lozano Y, Djordjevic A, Devata S, Matthews JP, Yedavalli S, Chejfec G . 1995 Int. J. Cancer 61: 104–109

  • Zigman JM, Westermark GT, LaMendola J, Boel E, Steiner DF . 1993 Endocrinology 133: 2508–2514

Download references

Acknowledgements

We thank Prof P Comoglio (University of Turin, Italy), Dr G Flatau (INSERM U452, Nice, France), Dr L Thim (Novo Nordisk, Bagsvaerd, Denmark), Prof B Westley (University of Newcastle, Newcastle upon Tyne NE1 4LP, UK) for providing reagents. We also acknowledge Dr J Courty (CRRET Laboratory, Creteil, France) for providing the LNCaP cell line. This work was supported by INSERM, the ‘Belgische Federatie tegen Kanker’, the ‘FORTIS Verrekeringen’, and the Fund for Scientific Research-Flanders (Brussels, Belgium).

Author information

Authors and Affiliations

  1. INSERM U482, Signal transduction and cellular functions in Diabetes and Digestive Cancers, Hôpital Saint-Antoine, Paris, Cedex 12, 75571, France

    Karine Régnauld, Quang-Dé Nguyen, Christian Gespach & Shahin Emami

  2. The Laboratory of Experimental Cancerology, Ghent University Hospital, Ghent, B-9000, Belgium

    Luc Vakaet, Erik Bruyneel & Marc Mareel

  3. CRC-Bernard, IFR6, Hôpital Lariboisière, Paris, Cedex 10, 75475, France

    Jean-Marie Launay

  4. Department of Biology, Faculty of Science,Chiba University, Inageku, 263-8522, Chiba, Japan

    Takeshi Endo

Authors
  1. Karine Régnauld
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Quang-Dé Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luc Vakaet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erik Bruyneel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Marie Launay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeshi Endo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marc Mareel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Gespach
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shahin Emami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shahin Emami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Régnauld, K., Nguyen, QD., Vakaet, L. et al. G-protein αolf subunit promotes cellular invasion, survival, and neuroendocrine differentiation in digestive and urogenital epithelial cells. Oncogene 21, 4020–4031 (2002). https://doi.org/10.1038/sj.onc.1205498

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205498

Keywords

This article is cited by

Search

Advanced search

Quick links