Role of nuclear ADAMTS-1 in normal and tumoral cells

• Grant number: 18/06334-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 15, 2018
• End date: February 14, 2019
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Suély Vieira da Silva
• Supervisor: Juan Carlos Rodríguez Manzaneque Escribano
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica (GENYO), Spain
• Associated to the scholarship: 15/09845-9 - Role of ADAMTS-1 (a Disintegrin and Metalloproteinase with Thrombospondin Motifs 1) in nucleus of normal and tumoral human breast cells, BP.DR

Abstract

Mammary tumors are the second most frequent type of neoplasm in worldwide among women. In extracellular matrix quantitative and qualitative changes occur resulting in remodeling, originated from the activity of proteases secreted by mammary cells in microenvironment. Metalloproteinases belonging to the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family are well known proteases secreted by cells with proteolytic activity on proteoglycans from extracellular matrix. However, our group observed for the first time this protease at the nuclei of the three mammary cell lines studied. Our data showed that ADAMTS-1 is located in nuclei of cells, while the other aggrecanases (ADAMTS-4 and ADAMTS-5) were located in cytoplasm and extracellular matrix. The ADAMTS-1 location was no longer nuclear when Golgi apparatus was disrupted with monensin, indicating that secretion is needed before ADAMTS-1 goes to the nuclei. We also detected that ADAMTS-1 is located at epithelial cells nuclei, but not on the nuclei of mesenchymal-derived cells. Further, we observed ADAMTS-1 secreted by epithelial cells is endocytosed by mesenchymal cells and goes to the nuclei. In this context, it is important to (1) understand how ADAMTS-1 reaches the nuclei and (2) identify partners in this subcellular compartment. The info obtained here will help us to understand ADAMTS-1 function in the nuclei and have potential to fill gaps of our present knowledge on fundamental cell biology processes such as protein secretion, endocytosis and nucleocytoplasmic transport. (AU)