| Grant number: | 17/22047-0 |
| Support type: | Regular Research Grants |
| Duration: | February 01, 2018 - January 31, 2021 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Guacyara da Motta |
| Grantee: | Guacyara da Motta |
| Home Institution: | Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil |
Abstract
Integrins are a superfamily of cell adhesion receptors that recognize ligands present in the extracellular matrix (ME) or associated with the cell surface. The activation of integrins triggers a variety of signal transduction events that modulate cellular behaviors such as adhesion, proliferation, survival or apoptosis, shape, polarity, mobility, haptotaxis, gene expression, and differentiation. The fibrinolysis is a process that controls hemostasis through the tissue plasminogen activator, which has ligands in the fibrin monomers, and the urokinase plasminogen activator (uPA) and its uPAR cell surface receptor are critical in directing ME degradation, which is the key to cellular phenomena of tissue invasion in angiogenesis and inflammation. Proteoglycans are glycoproteins that exhibit one or more protein chain associated glycosaminoglycans chains and heparan sulfate proteoglycans (PGHS) are transmembrane structures that play an important role in cell adhesion, and may associate with other receptors, influencing their functions, especially the integrins and the receptors of the growth factors. The human plasma kallikrein-kinin system (SCC) refers to the release of bradykinin (BK) from high molecular weight kininogen (H-kininogen) by plasma kallikrein (hKB1) with high specificity. The pro-hKB1 associated cell surface can be activated and release BK from the H-kininogen and can activate pro-uPA; H-kininogen without BK (HKa) when associated with uPAR, or vitronectin, is antiangiogenic because it blocks uPA/uPAR mediated signaling. The PGHS mediates H-kininogen and pro-hKB1 endocytosis; the uPA/PAI-1/uPAR complex is internalized by CD91. Cell adhesion is a necessary phenomenon for both anchorage and mediate a wide diversity of phenotypic responses of the cellular microenvironment and to determine how adhesion receptors regulate chemical signals through the control of the space-time organization of enzymes and adapters is important mainly considering the process of tumor progression. The overall objective of the present project will be to study in breast cancer the interaction between integrins and uPAR by checking the influence of SCC proteins and proteoglycans in this interaction. We will try to study how the proteins from both SCC and SAP may interact in breast cancer cell lines. (AU)