Characterization of the role of non-catalytic domains of ADAM17 in events involved in cancer development

Abstract

The ADAMs with an increased expression in several types of cancer including squamous cell carcinoma of head and neck. Because of this and that these proteases modulate, the ADAMs have long been associated with the process of carcinogenesis. The ADAMs are the major proteases responsible for releasing ectodomínios cell surface proteins, thus mediating signal transduction such as EGFR. The ADAMs are Metalloproteinases composed generally by six conserved domains similar to Metalloproteinases of snake venom (metalloproteinase, disintegrina-type domains, rich in cysteines, epidermal growth factor type, transmembrane and cytoplasmic domain). However, little is known about the activities of the disintegrina-type domains and rich in cysteines in ADAM17 interaction with ligands and their specificity. During the stage of scientific initiation Fellowship candidate Frederick Padovan Borges, the test was observed by double-hybrid interaction of these domains with the vascular endothelium growth factor B (VEGF-B). This interaction indicates a possible role of disintegrina-type domains and rich in cysteines in the process of angiogenesis, which is crucial for the development of cancer. Thereby, this project proposes to continue this study characterizing the functional role of these domains in the interaction between ADAM17 and VEGF-B. For this there will be pull-down techniques, solid phase assays and co-imunopr