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Cholecystokinin-2 receptor modulates cell adhesion through β1-integrin in human pancreatic cancer cells

Oncogene volume 25, pages 4421–4428 (2006)Cite this article

Abstract

Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a ‘cancer gene array’ and identified β1-integrin subunit as a new gastrin-regulated gene in human pancreatic cancer cells. We also demonstrated that Src family kinases and the phosphatidylinositol-3-kinase (PI-3-kinase) pathway play a crucial role in the expression of β1-integrin induced by gastrin. Our results also showed that gastrin modulates cell–substrate adhesion via β1-integrin. Indeed, using blocking anti-β1-integrin monoclonal antibodies, we completely reversed the increase in cell–substrate adhesion induced by gastrin. In addition, we observed that in response to gastrin, β1-integrin is tyrosine phosphorylated by Src family kinases and associates with paxillin, a scaffold protein involved in focal adhesion and integrin signalling. This mechanism might be involved in gastrin-induced cell adhesion. Moreover, we showed in vivo that targeted CCK2R expression in the pancreas of Elas-CCK2 mice leads to the overexpression of β1-integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.

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References

  • Aly A, Shulkes A, Baldwin GS . (2004). Biochim Biophys Acta 1704: 1–10.

  • Bierkamp C, Bonhoure S, Mathieu A, Clerc P, Fourmy D, Pradayrol L et al. (2004). Am J Pathol 165: 2135–2145.

  • Bierkamp C, Kowalski-Chauvel A, Dehez S, Fourmy D, Pradayrol L, Seva C . (2002). Oncogene 21: 7656–7670.

  • Butler B, Blystone SD . (2005). J Biol Chem 280: 14556–14562 (Epub 2005 Feb 6).

  • Calderwood DA . (2004). J Cell Sci 117: 657–666.

  • Calderwood DA, Fujioka Y, de Pereda JM, Garcia-Alvarez B, Nakamoto T, Margolis B et al. (2003). Proc Natl Acad Sci USA 100: 2272–2277.

  • Caplin M, Savage K, Khan K, Brett B, Rode J, Varro A et al. (2000). Br J Surg 87: 1035–1040.

  • Chao JT, Martinez-Lemus LA, Kaufman SJ, Meininger GA, Ramos KS, Wilson E . (2005). Am J Physiol Cell Physiol.

  • Chiu SJ, Jiang ST, Wang YK, Tang MJ . (2002). J Biomed Sci 9: 261–272.

  • Clark EA, Brugge JS . (1995). Science 268: 233–239.

  • Clerc P, Leung-Theung-Long S, Wang TC, Dockray GJ, Bouisson M, Delisle MB et al. (2002). Gastroenterology 122: 428–437.

  • Colucci R, Blandizzi C, Tanini M, Vassalle C, Breschi MC, Del Tacca M . (2005). Br J Pharmacol 144: 338–348.

  • Daulhac L, Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C . (1999a). FEBS Lett 445: 251–255.

  • Daulhac L, Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C . (1999b). J Biol Chem 274: 20657–20663.

  • de Weerth A, von Schrenck T, Lohr M, Mirau S, Greten H, Kalthoff H . (1999). Hepatogastroenterology 46: 472–478.

  • Eliceiri BP, Cheresh DA . (2000). Cancer J 6: S245–S249.

  • Felsenfeld DP, Schwartzberg PL, Venegas A, Tse R, Sheetz MP . (1999). Nat Cell Biol 1: 200–206.

  • Ferrand A, Kowalski-Chauvel A, Bertrand C, Escrieut C, Mathieu A, Portolan G et al. (2005). J Biol Chem 280: 10710–10715.

  • Ferrand A, Kowalski-Chauvel A, Bertrand C, Pradayrol L, Fourmy D, Dufresne M et al. (2004). Exp Cell Res 301: 128–138.

  • Fontana MG, Donato F, Villanacci V, Ghirardi M, Moneghini D, Di Betta E et al. (1999). Eur Surg Res 31: 406–411.

  • Fukui H, Kinoshita Y, Maekawa T, Okada A, Waki S, Hassan S et al. (1998). Gastroenterology 115: 1483–1493.

  • Funahashi H, Takeyama H, Sawai H, Furuta A, Sato M, Okada Y et al. (2003). Pancreas 27: 190–196.

  • Gao C, Schaefer E, Lakkis M, Blystone SD . (2005). J Biol Chem 280: 15422–15429 (Epub 2005 Feb 7).

  • Giancotti FG, Tarone G . (2003). Annu Rev Cell Dev Biol 19: 173–206.

  • Grippo PJ, Nowlin PS, Demeure MJ, Longnecker DS, Sandgren EP . (2003). Cancer Res 63: 2016–2019.

  • Guo W, Giancotti FG . (2004). Nat Rev Mol Cell Biol 5: 816–826.

  • Guo YS, Cheng JZ, Jin GF, Gutkind JS, Hellmich MR, Townsend Jr CM . (2002). J Biol Chem 277: 48755–48763.

  • Halatsch ME, Hirsch-Ernst KI, Kahl GF, Weinel RJ . (1997). Cancer Lett 118: 7–11.

  • Hocker M . (2004). Ann NY Acad Sci 1014: 97–109.

  • Jenkins AL, Nannizzi-Alaimo L, Silver D, Sellers JR, Ginsberg MH, Law DA et al. (1998). J Biol Chem 273: 13878–13885.

  • Kaufmann R, Schafberg H, Rudroff C, Henklein P, Nowak G . (1997). Neuropeptides 31: 573–583.

  • Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C . (1996). J Biol Chem 271: 26356–26361.

  • Lohr M, Trautmann B, Gottler M, Peters S, Zauner I, Maier A et al. (1996). Pancreas 12: 248–259.

  • Noble PJ, Wilde G, White MR, Pennington SR, Dockray GJ, Varro A . (2003). Am J Physiol Gastrointest Liver Physiol 284: G75–G84.

  • Playford MP, Schaller MD . (2004). Oncogene 23: 7928–7946.

  • Prasad NB, Biankin AV, Fukushima N, Maitra A, Dhara S, Elkahloun AG et al. (2005). Cancer Res 65: 1619–1626.

  • Ross RS . (2004). Cardiovasc Res 63: 381–390.

  • Shimoyama S, Gansauge F, Gansauge S, Oohara T, Beger HG . (1995). Int J Pancreatol 18: 227–234.

  • Sinclair NF, Ai W, Raychowdhury R, Bi M, Wang TC, Koh TJ et al. (2004). Am J Physiol Gastrointest Liver Physiol 286: G992–G992.

  • Slice LW, Hodikian R, Zhukova E . (2003). J Cell Physiol 196: 454–463.

  • Smith JP, Fantaskey AP, Liu G, Zagon IS . (1995). Am J Physiol 268: R135–R141.

  • Smith JP, Hamory MW, Verderame MF, Zagon IS . (1998). Int J Mol Med 2: 309–315.

  • Smith JP, Shih A, Wu Y, McLaughlin PJ, Zagon IS . (1996). Am J Physiol 270: R1078–R1084.

  • Smith JP, Verderame MF, Zagon IS . (1999). Cancer Lett 135: 107–112.

  • Stepan VM, Dickinson CJ, del Valle J, Matsushima M, Todisco A . (1999a). Am J Physiol 276: G1363–G1372.

  • Stepan VM, Tatewaki M, Matsushima M, Dickinson CJ, del Valle J, Todisco A . (1999b). Am J Physiol 276: G415–G424.

  • Taniguchi T, Matsui T, Ito M, Murayama T, Tsukamoto T, Katakami Y et al. (1994). Oncogene 9: 861–867.

  • Taniguchi T, Takaishi K, Murayama T, Ito M, Iwata N, Chihara K et al. (1996). Oncogene 12: 1357–1360.

  • Todisco A, Takeuchi Y, Urumov A, Yamada J, Stepan VM, Yamada T . (1997). Am J Physiol 273: G891–G898.

  • Turner CE . (2000). J Cell Sci 113 (Part 23): 4139–4140.

  • van der Flier A, Sonnenberg A . (2001). Cell Tissue Res 305: 285–298.

  • Wagner M, Luhrs H, Kloppel G, Adler G, Schmid RM . (1998). Gastroenterology 115: 1254–1262.

  • Wang JY, Wang H, Johnson LR . (1995). Am J Physiol 269: C1474–C1481.

  • Wroblewski LE, Pritchard DM, Carter S, Varro A . (2002). Biochem J 365: 873–879.

  • Zhukova E, Sinnett-Smith J, Wong H, Chiu T, Rozengurt E . (2001). J Cell Physiol 189: 291–305.

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Acknowledgements

This work was supported by funds from INSERM, The ‘Association pour la Recherche contre le Cancer’ Grants ARC #3664, the ‘Ligue contre le Cancer’ Région Midi-Pyrénées and ACI FNS 2001#1A067G.

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Authors and Affiliations

  1. INSERM U 531, IFR 31, Institut Louis Bugnard, Toulouse, France

    C Cayrol, P Clerc, C Bertrand, V Gigoux, D Fourmy, M Dufresne & C Seva

  2. Histology Facility, IFR 31, Institut Louis Bugnard, Toulouse, France

    G Portolan

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  1. C Cayrol
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  2. P Clerc
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  3. C Bertrand
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  4. V Gigoux
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  5. G Portolan
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  6. D Fourmy
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  7. M Dufresne
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  8. C Seva
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Correspondence to C Seva.

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Cayrol, C., Clerc, P., Bertrand, C. et al. Cholecystokinin-2 receptor modulates cell adhesion through β1-integrin in human pancreatic cancer cells. Oncogene 25, 4421–4428 (2006). https://doi.org/10.1038/sj.onc.1209484

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