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Nuclear ADAMTS-1 regulating normal and cancer cells

Grant number: 18/05566-6
Support type:Regular Research Grants
Duration: August 01, 2018 - July 31, 2020
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Vanessa Morais Freitas
Grantee:Vanessa Morais Freitas
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer is the leading cause of death in economically developed countries and the leading cause of death in developing countries. The tumor occurs from a progressive succession of genetic alterations, each conferring a more potent growth type, leading to a progressive conduction of the normal cells in cells with malignant phenotype. The microenvironments in which the tumors develop may be regular aspects of the tumor such as angiogenesis, invasion and metastasis. This microenvironment consists of tumor stromal components, fibroblasts, endothelial cells, immune system cells, extracellular matrix proteins and proteoglycans, growth factors, and proteases that remodel these components. ADAMTS (a disintegrin and metalloproteinase with thrombospondin or adamalysin-thrombospondin motifs) are extracellular matrix metalloproteinases enzymes related to collagen processing, matrix proteoglycan cleavage, angiogenesis, von Willebrand factor cleavage, inflammation, organogenesis, and fertility. Although described as an extracellular protease, data published by our laboratory show that by both immunolocalization and immunoblott that ADAMTS-1 is present in the nucleus of three human mammary cell lines (MCF-10A, MCF-7 and MDA-MB- 231). In addition to our data, there are no other papers describing ADAMTS members in the nucleus, however literature data show that other matrix metalloproteases, MMP-2, MMP-3 and MMP inhibitor, TIMP-1 have already been observed in the nucleus of different cells. Thus, we intend to evaluate how ADAMTS-1 reaches the nucleus and if this protease presence in this cellular compartment is involved morphological changes or basic cell functions such as proliferation and migration. 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)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NORIEGA-GUERRA, HEYDI; FREITAS, VANESSA MORAIS. Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 11 NOV 2018. Web of Science Citations: 4.

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