THE ROLE OF LGR6 POSITIVE STEM CELLS IN LUNG ADENOCARCINOMA
Lung cancer is the major cause of cancer-related deaths in developed countries. In the last decades, important advances have been made in this field, but understanding of the cellular and molecular components is still the main priority. Ventura and colleagues have previously described Lgr6 as a lung stem cells marker. Lgr6+ cells showed ability of self-renewal and differentiation, but also an higher tumorigenic potential. In particular, during lung adenocarcinoma progression, Lgr6+ cells number tend to increase and higher levels of miR-19 (miR-17-92 cluster) and reduced p38a protein levels were observed. These alterations support the survival of Lgr6+ cells, mediated by increased Wnt/b-Catenin activity. The project of my PhD thesis will be focused on the functional and molecular characterization of Lgr6+ cells. Tumorigenicity, invasion and metastatic potential will be investigated using several in vitro and in vivo techniques. In order to define the tumor growth rate, the stem cell differentiation and the genetic expression profile of Lgr6+ cells, at different stages of cancer development, ex-vivo analysis on mouse and human lung explants will be performed. The final outcome of these investigations will produce pivotal information about the process of malignization in lung adenocarcinoma progression context, with high potential to translate in to the clinic and for future testing and assessment of therapeutic drugs to treat lung cancer.