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  • 1.
    Gramolelli, Silvia
    et al.
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Cheng, Jianpin
    CHU Vaudois, Dept Oncol, Lausanne, Switzerland;Univ Lausanne, Lausanne, Switzerland;Ludwig Inst Canc Res, Lausanne, Switzerland.
    Martinez-Corral, Ines
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Vaha-Koskela, Markus
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Elbasani, Endrit
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Kaivanto, Elisa
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Rantanen, Ville
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland.
    Tuohinto, Krista
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Hautaniemi, Sampsa
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland.
    Bower, Mark
    Chelsea & Westminster Hosp, London, England;Imperial Coll London, London, England.
    Haglund, Caj
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland;Univ Helsinki, Dept Surg, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Univ Helsinki, Dept Pathol, Helsinki, Finland.
    Alitalo, Kari
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland.
    Mäkinen, Taija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Petrova, Tatiana V.
    CHU Vaudois, Dept Oncol, Lausanne, Switzerland;Univ Lausanne, Lausanne, Switzerland;Ludwig Inst Canc Res, Lausanne, Switzerland.
    Lehti, Kaisa
    Univ Helsinki, Genome Scale Biol, Res Programs Unit, Helsinki, Finland;Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden.
    Ojala, Paivi M.
    Univ Helsinki, Translat Canc Biol, Res Programs Unit, Helsinki, Finland;Imperial Coll London, Dept Med, Div Infect Dis, Sect Virol, London, England;Fdn Finnish Canc Inst, Helsinki, Finland.
    PROX1 is a transcriptional regulator of MMP142018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, article id 9531Article in journal (Refereed)
    Abstract [en]

    The transcription factor PROX1 is essential for development and cell fate specification. Its function in cancer is context-dependent since PROX1 has been shown to play both oncogenic and tumour suppressive roles. Here, we show that PROX1 suppresses the transcription of MMP14, a metalloprotease involved in angiogenesis and cancer invasion, by binding and suppressing the activity of MMP14 promoter. Prox1 deletion in murine dermal lymphatic vessels in vivo and in human LECs increased MMP14 expression. In a hepatocellular carcinoma cell line expressing high endogenous levels of PROX1, its silencing increased both MMP14 expression and MMP14-dependent invasion in 3D. Moreover, PROX1 ectopic expression reduced the MMP14-dependent 3D invasiveness of breast cancer cells and angiogenic sprouting of blood endothelial cells in conjunction with MMP14 suppression. Our study uncovers a new transcriptional regulatory mechanism of cancer cell invasion and endothelial cell specification.

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