PROX1 is a transcriptional regulator of MMP14
| Autor: | Päivi M. Ojala, Kaisa Lehti, Ville Rantanen, Sampsa Hautaniemi, Kari Alitalo, Tatiana V. Petrova, Mark Bower, Ines Martinez-Corral, Endrit Elbasani, Markus Vähä-Koskela, Jianpin Cheng, Krista Tuohinto, Elisa Kaivanto, Taija Makinen, Caj Haglund, Silvia Gramolelli |
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| Přispěvatelé: | St Stephen's Aids Trust, Research Programs Unit, Translational Cancer Biology (TCB) Research Programme, University of Helsinki, Genome-Scale Biology (GSB) Research Program, Medicum, Sampsa Hautaniemi / Principal Investigator, Bioinformatics, Department of Biochemistry and Developmental Biology, Clinicum, Department of Surgery, II kirurgian klinikka, Department of Pathology, Kari Alitalo / Principal Investigator, Kaisa Irene Lehti / Principal Investigator, HUS Abdominal Center |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcription Genetic Angiogenesis HUMAN BREAST-CANCER Cell- och molekylärbiologi PROGRESSION Gene Knockout Techniques Mice TYPE-1 MATRIX-METALLOPROTEINASE HEPATOCELLULAR-CARCINOMA MT1-MMP LYMPHATIC ENDOTHELIAL-CELLS Promoter Regions Genetic Multidisciplinary Lymphangiogenesis Endothelial stem cell Multidisciplinary Sciences Medicine Science & Technology - Other Topics LYMPHANGIOGENESIS EXPRESSION Science Cell fate determination Biology Article Cell Line 03 medical and health sciences Matrix Metalloproteinase 14 Gene silencing Animals Humans Transcription factor Lymphatic Vessels Homeodomain Proteins Cancer och onkologi Science & Technology Tumor Suppressor Proteins Endothelial Cells GENE HOMEOBOX PROTEIN 030104 developmental biology Cancer and Oncology Cancer cell Cancer research Endothelial Cells/metabolism Endothelial Cells/pathology Homeodomain Proteins/genetics Homeodomain Proteins/metabolism Lymphatic Vessels/metabolism Matrix Metalloproteinase 14/genetics Promoter Regions Genetic/genetics Tumor Suppressor Proteins/deficiency Tumor Suppressor Proteins/genetics Tumor Suppressor Proteins/metabolism Ectopic expression 3111 Biomedicine Cell and Molecular Biology |
| Zdroj: | Scientific reports, vol. 8, no. 1, pp. 9531 Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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