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PROX1 is a transcriptional regulator of MMP14

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Title: PROX1 is a transcriptional regulator of MMP14
Authors: 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
Lehti, K
Ojala, PM
Item Type: Journal Article
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.
Issue Date: 22-Jun-2018
Date of Acceptance: 7-Jun-2018
URI: http://hdl.handle.net/10044/1/61151
DOI: https://dx.doi.org/10.1038/s41598-018-27739-w
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre- ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per- mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: St Stephen's Aids Trust
Funder's Grant Number: N/A
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
TYPE-1 MATRIX-METALLOPROTEINASE
LYMPHATIC ENDOTHELIAL-CELLS
HUMAN BREAST-CANCER
HEPATOCELLULAR-CARCINOMA
HOMEOBOX PROTEIN
EXPRESSION
MT1-MMP
GENE
LYMPHANGIOGENESIS
PROGRESSION
Publication Status: Published
Article Number: 9531
Appears in Collections:Department of Medicine (up to 2019)