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

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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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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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