FIBRONECTIN-BINDING INTEGRINS PARTICIPATE IN THE CONTROL OF GEF-H1 ACTIVATION AND ITS ROLE IN BREAST CANCER

FERNÁNDEZ CHÁVEZ, L.; BERMÚDEZ, V.; ALONSO, E.G.; SCHWEITZER, K.; FERRONATO, M.J.; FERMENTO, M.E.; ALONSO, E.N.; FACCHINETTI, M.M.; CURINO, A.C.; COLÓ, G.P.

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Rho family of small GTPases plays a crucial role in several biological processes and cycles between on and off states. This switch is controlled by GEFs (Rho-activators) and GAPs (Rho-inhibitors).We have previously identified by Mass Spectrometry (MS) analysis that GEF-H1 is the major GEF that activates RhoA and we observed a significant GEF-H1 overexpression in human breast cancer biopsies compared with normal breast tissue.The aim of this work is to study the role of GEF-H1 depletion in tumor development and the mechanism of GEF-H1 fibronectin (FN)-binding integrins dependent activation .Using CRISPR/Cas9 technology, we generated GEF-H1-knock out (KO) cells in a murine invasive breast cancer cell line (LM3). GEF-H1-KO cells were implanted subcutaneously in the mammary fat pad of BALB/c mice, showing a significant decrease in tumor formation (n=14, p