PROX1 is a transcriptional regulator of MMP14

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Gramolelli , S , Cheng , J , Martinez-Corral , I , Vähä-Koskela , M , Elbasani , E , Kaivanto , E , Rantanen , V , Tuohinto , K , Hautaniemi , S , Bower , M , Haglund , C , Alitalo , K , Mäkinen , T , Petrova , T V , Lehti , K & Ojala , P M 2018 , ' PROX1 is a transcriptional regulator of MMP14 ' , Scientific Reports , vol. 8 , 9531 . https://doi.org/10.1038/s41598-018-27739-w

Title: PROX1 is a transcriptional regulator of MMP14
Author: Gramolelli, Silvia; Cheng, Jianpin; Martinez-Corral, Ines; Vähä-Koskela, Markus; Elbasani, Endrit; Kaivanto, Elisa; Rantanen, Ville; Tuohinto, Krista; Hautaniemi, Sampsa; Bower, Mark; Haglund, Caj; Alitalo, Kari; Mäkinen, Taija; Petrova, Tatiana V.; Lehti, Kaisa; Ojala, Päivi M.
Other contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Translational Cancer Biology (TCB) Research Programme
University of Helsinki, Translational Cancer Biology (TCB) Research Programme
University of Helsinki, Kaisa Irene Lehti / Principal Investigator
University of Helsinki, Medicum














Date: 2018-06-22
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-27739-w
URI: http://hdl.handle.net/10138/237191
Abstract: 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.
Subject: TYPE-1 MATRIX-METALLOPROTEINASE
LYMPHATIC ENDOTHELIAL-CELLS
HUMAN BREAST-CANCER
HEPATOCELLULAR-CARCINOMA
HOMEOBOX PROTEIN
EXPRESSION
MT1-MMP
GENE
LYMPHANGIOGENESIS
PROGRESSION
3111 Biomedicine
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