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Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion

Oncogene volume 29, pages 6452–6463 (2010)Cite this article

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Abstract

The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.

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Acknowledgements

We thank Professor J Ylänne and Professor M Salmi for critically reviewing the paper; J Siivonen, H Marttila, O Levälampi and P Terho for the excellent technical assistance. This study has been supported by Academy of Finland, ERC Starting Grant, Sigrid Juselius Foundation, EMBO YIP and Finnish Cancer Organizations. JN has been supported by Maud Kuistila Memorial Foundation and Turku University Foundation. JN, ST and TP were supported by Turku Graduate School of Biomedical Sciences and AM by Drug Discovery Graduate School.

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Authors and Affiliations

  1. Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland

    J Nevo, A Mai, S Tuomi, T Pellinen & J Ivaska

  2. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

    J Nevo, A Mai, S Tuomi, T Pellinen & J Ivaska

  3. Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, Jyväskylä, Finland

    O T Pentikäinen

  4. Department of Pathology, Helsinki University Hospital, Helsinki, Finland

    P Heikkilä

  5. Department of Oncology, Helsinki University Hospital, Helsinki, Finland

    J Lundin, H Joensuu & P Bono

  6. Department of Biochemistry and Food chemistry, University of Turku, Turku, Finland

    J Ivaska

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  1. J Nevo
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Correspondence to J Ivaska.

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Nevo, J., Mai, A., Tuomi, S. et al. Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion. Oncogene 29, 6452–6463 (2010). https://doi.org/10.1038/onc.2010.376

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