Role of the IQGAP1 scaffold protein in thyroid cancer

Resumen del póster presentado al 6th Symposium on Biomedical Research: Advances and Perspectives in Molecular Endocrinology "In Homage to Gabriella Morreale", celebrado en el Instituto de Investigaciones Biomédicas Alberto Sols (IIBM-CSIC) el 31 de mayo de 2019.The IQGAP family of scaffold proteins comprises three members which have been described to interact with numerous proteins in several biological processes and participate in the signaling cascade of multiple pathways. Among these proteins IQGAP1 has been the most deeply studied, having characterized its function as a scaffold protein in the MAPK pathway and its interaction with actin leading to regulation of the cytoskeleton. Because of these functions it has been studied in multiple malignancies, where it has been assigned a tumorigenic effect. We have studied IQGAP1 expression using different stablished cell lines of human thyroid carcinomas. Our results indicate that these carcinoma cell lines have variable levels of IQGAP1 but in general these levels are higher when compared to the normal thyroid cell line control. The results obtained are in agreement with the TCGA and Oncomine databases. Using IQGAP1 silenced cell lines we tried to elucidate how this protein was affecting tumor hallmarks such as proliferation, invasion, cell migration and epithelial mesenchymal transition. The effects of silencing IQGAP1 were different depending on the cell line and the oncogenic signature. While in some of them silencing produced an increase in the migration rate of the cells, others had the opposite behavior. We also found these differences when studying EMT markers such as E-cadherin and N-cadherin. Furthermore, cell viability was unaffected by IQGAP1 silencing and consequently the size of the primary tumor was not altered when cells were xenografted in a chicken embryo model. Importantly IQGAP1 silencing greatly decreased the ability of the tumor cells to intravasate and metastasize to distant organs such as lungs and brain. Further studies will focus on trying to discover the underlying mechanisms responsible for the differences observed between cell lines. Our results indicate a role forIQGAP1 in thyroid tumorigenesis and underscore the importance of defining the oncogenic signature and particularities of a given tumor type in order to design effective therapeutic strategies.This work was supported by grants SAF2016-75531-R from MINECO, Spain and PI14/01980 from ISCIII, Spain (FEDER); B2017/BMD-3724 from CAM and GCB14142311CRES from AECC.Peer reviewe