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p63 controls cell migration and invasion by transcriptional regulation of MTSS1

Oncogene volume 35, pages 1602–1608 (2016)Cite this article

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Abstract

Metastasis is a multistep cell-biological process, which is orchestrated by many factors, including metastasis activators and suppressors. Metastasis Suppressor 1 (MTSS1) was originally identified as a metastasis suppressor protein whose expression is lost in metastatic bladder and prostate carcinomas. However, recent findings indicate that MTSS1 acts as oncogene and pro-migratory factor in melanoma tumors. Here, we identify and characterized a molecular mechanism controlling MTSS1 expression, which impinges on a pro-tumorigenic role of MTSS1 in breast tumors. We found that in normal and in cancer cell lines ΔNp63 is able to drive the expression of MTSS1 by binding to a p63-binding responsive element localized in the MTSS1 locus. We reported that ΔNp63 is able to drive the migration of breast tumor cells by inducing the expression of MTSS1. Notably, in three human breast tumors data sets the MTSS1/p63 co-expression is a negative prognostic factor on patient survival, suggesting that the MTSS1/p63 axis might be functionally important to regulate breast tumor progression.

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Acknowledgements

We thank the laboratory members for helpful discussion. This work has been supported by MFAG AIRC 15523 grant awarded to AP, and by Medical Research Council (UK), Ministry of Health ‘Rc1.1’ and ‘Rc 1.3’, AIRC Grant IG-15653, AIRC 5xmille (#9979), ‘NCDs Fondazione Roma’ grant awarded to GM.

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Authors and Affiliations

  1. Department of Experimental Medicine and Surgery, University of Rome ‘Tor Vergata’, Rome, Italy

    A Giacobbe, M Compagnone, L Bongiorno-Borbone & G Melino

  2. Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK

    A Antonov & G Melino

  3. The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ, USA

    E K Markert

  4. Department of Human Genetics, Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands

    J H Zhou

  5. Biochemistry Laboratory IDI-IRCCS c/o Department of Experimental Medicine and Surgery, University of Rome ‘Tor Vergata’, Rome, Italy

    M Annicchiarico-Petruzzelli

  6. Institute of Cell Biology and Neurobiology (IBCN), CNR, Rome, Italy

    A Peschiaroli

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  1. A Giacobbe
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Correspondence to G Melino or A Peschiaroli.

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Giacobbe, A., Compagnone, M., Bongiorno-Borbone, L. et al. p63 controls cell migration and invasion by transcriptional regulation of MTSS1. Oncogene 35, 1602–1608 (2016). https://doi.org/10.1038/onc.2015.230

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