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The cancer chemopreventive agent resveratrol induces tensin, a cell–matrix adhesion protein with signaling and antitumor activities

Oncogene volume 24, pages 3274–3284 (2005)Cite this article

Abstract

During a search to identify resveratrol (3,5,4′-trihydroxy-trans-stilbene, RV) target genes in the human erythroleukemic K562 cell line, we show here that the tensin gene and protein levels are remarkably induced by this dietary polyphenol. Tensin, a cell–matrix adhesion protein binding the integrins and cytoskeletal actin filaments also interacts with PI3-kinase and JNK signaling pathways. Tensin induction by RV is associated with increased K562 cell adhesion to fibronectin, cell spreading and actin polymerization. The same responses were observed in the tensin-deficient MCF7 human breast cancer cell line. In K562 and MCF7 cells treated by RV, tensin was found in punctate and intracytoplasmic areas. In MCF7 epithelial cells, induction of tensin is not exclusively associated with plasma membrane-bound vinculin, suggesting a dual localization of tensin in both focal and fibrillar adhesions. Pharmacological blockade of PI3-kinase and Rho GTPases/Rho-kinase resulted in selective depletion of focal adhesions, disorganization of tensin localization and disruption of stress fibers. RV increased cell motility and attachment to fibronectin in MCF7 cells submitted to mechanical laminar flow stress, and abrogated estrogen-induced MCF7 cancer cell invasion. Our data support the conclusion that induction of tensin by RV contributes to the chemopreventive and anti-invasive activity of this natural dietary compound in tensin-negative and -deficient leukemic cells or epithelioid cancers.

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Acknowledgements

We would like to express our gratitude to Dr Lo for providing the polyclonal human anti-tensin antibody. We also acknowledge Evelyne Souil (Plate-Forme d'Histologie, Institut Cochin) for her help in adhesion and immunofluorescence studies. We thank Nicole Arous for assistance in the RFDD approach and Frank Letourneur and Nicolas Lebrun for cDNA sequencing. This study was supported by INSERM, FORTIS Bank, and a postdoctoral fellowship, from Aventis (CMR).

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  1. Christian Gespach and Marie-Claude Garel: These authors contributed equally to this work

Authors and Affiliations

  1. INSERM U567 – UMR 8104 – Département d'Hématologie, Institut Cochin, Université Paris V, Maternité Port-Royal, 123 boulevard de Port-Royal, Paris, 75014, France

    Christelle M Rodrigue, Françoise Porteu, Nicole Navarro, Paul-Henri Romeo & Marie-Claude Garel

  2. Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintalaan 185, Gent, B-9000, Belgium

    Erik Bruyneel & Marc Bracke

  3. INSERM U673, Cancérologie Fondamentale et clinique des Tumeurs Solides Humaines, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, Paris, 75571, France

    Christelle M Rodrigue & Christian Gespach

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  1. Christelle M Rodrigue
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Correspondence to Christian Gespach.

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Rodrigue, C., Porteu, F., Navarro, N. et al. The cancer chemopreventive agent resveratrol induces tensin, a cell–matrix adhesion protein with signaling and antitumor activities. Oncogene 24, 3274–3284 (2005). https://doi.org/10.1038/sj.onc.1208485

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