Función del RalGDS en cáncer asociado a colitis y en el desarrollo de la céluta T

Abstract

31 RalGDS is one of the proteins that mediate the activation of the small G protein Ral downstream of the Ras GTPase. Ral has several functions in oncogenesis and vesicle transport and it also participates in different processes within the immune system. Cancer and inflammation are two processes highly related in several diseases, such as colitis-associated cancer. Our aim in this project was to analyze the role of the RalGDS/Ral pathway in colitis-associated cancer studying the effects in colon carcinogenesis and in colon inflammation. Here, we show that RalGDS regulates colitis-associated cancer by modulating colon inflammation. Our results demonstrate that RalGDS participates in colon acute inflammation through different cells in different stages of the disease. RalGDS is necessary for the inflammatory response in early stages of the colon inflammation probably acting through the CD4+ T cells of the lamina propria. However, RalGDS is also essential in myeloid cells for the resolution of the colon inflammation. Our research shows new data about the importance of the RalGDS/Ral pathway in an in vivo model of inflammation-associated cancer. Additionally to this study, we have also analyzed the function of the protein RalGDS in the development of the T cell in the thymus. Previous work in our group has demonstrated that Ral GTPases, activated by RalGDS protein, regulate cell-mediated cytotoxicity in NK cells and CD8+ cells. Our aim was to analyze the role of the RalGDS/Ral pathway in the functionality of the T cell and its development in the thymus. Here we show that the lack of RalGDS provokes a defect in positive and negative selection during thymocyte development. This developmental block does not result in fewer cells in periphery due to compensatory mechanisms. The absence of RalGDS is affecting the TCR signaling pathway. Our research shows an unknown role for the protein RalGDS in the development of the T cell.