PROX1 is a transcriptional regulator of MMP14

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 metalloprote...

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Autores principales:	Silvia Gramolelli, Jianpin Cheng, Ines Martinez-Corral, Markus Vähä-Koskela, Endrit Elbasani, Elisa Kaivanto, Ville Rantanen, Krista Tuohinto, Sampsa Hautaniemi, Mark Bower, Caj Haglund, Kari Alitalo, Taija Mäkinen, Tatiana V. Petrova, Kaisa Lehti, Päivi M. Ojala
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/192992a1a2db4e9fbb8ce454544679b2
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spelling	oai:doaj.org-article:192992a1a2db4e9fbb8ce454544679b22021-12-02T15:08:27ZPROX1 is a transcriptional regulator of MMP1410.1038/s41598-018-27739-w2045-2322https://doaj.org/article/192992a1a2db4e9fbb8ce454544679b22018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27739-whttps://doaj.org/toc/2045-2322Abstract 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.Silvia GramolelliJianpin ChengInes Martinez-CorralMarkus Vähä-KoskelaEndrit ElbasaniElisa KaivantoVille RantanenKrista TuohintoSampsa HautaniemiMark BowerCaj HaglundKari AlitaloTaija MäkinenTatiana V. PetrovaKaisa LehtiPäivi M. OjalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Silvia Gramolelli Jianpin Cheng Ines Martinez-Corral Markus Vähä-Koskela Endrit Elbasani Elisa Kaivanto Ville Rantanen Krista Tuohinto Sampsa Hautaniemi Mark Bower Caj Haglund Kari Alitalo Taija Mäkinen Tatiana V. Petrova Kaisa Lehti Päivi M. Ojala PROX1 is a transcriptional regulator of MMP14
description	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.
format	article
author	Silvia Gramolelli Jianpin Cheng Ines Martinez-Corral Markus Vähä-Koskela Endrit Elbasani Elisa Kaivanto Ville Rantanen Krista Tuohinto Sampsa Hautaniemi Mark Bower Caj Haglund Kari Alitalo Taija Mäkinen Tatiana V. Petrova Kaisa Lehti Päivi M. Ojala
author_facet	Silvia Gramolelli Jianpin Cheng Ines Martinez-Corral Markus Vähä-Koskela Endrit Elbasani Elisa Kaivanto Ville Rantanen Krista Tuohinto Sampsa Hautaniemi Mark Bower Caj Haglund Kari Alitalo Taija Mäkinen Tatiana V. Petrova Kaisa Lehti Päivi M. Ojala
author_sort	Silvia Gramolelli
title	PROX1 is a transcriptional regulator of MMP14
title_short	PROX1 is a transcriptional regulator of MMP14
title_full	PROX1 is a transcriptional regulator of MMP14
title_fullStr	PROX1 is a transcriptional regulator of MMP14
title_full_unstemmed	PROX1 is a transcriptional regulator of MMP14
title_sort	prox1 is a transcriptional regulator of mmp14
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/192992a1a2db4e9fbb8ce454544679b2
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PROX1 is a transcriptional regulator of MMP14

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