The leading cause of death in lung cancer patients is not the primary tumors but metastatic spreading of tumor cells in distant organs. Therefore, elucidating the molecular and cellular mechanisms of tumor metastasis represents the major task of lung cancer research. To successfully develop metastatic lesions, tumor cells have to exhibit plasticity to adapt to the changing microenvironment that they encounter at both the primary and distant sites. Epithelial to mesenchymal transition (EMT) represents one of major mechanisms throught which malignant tumor cells gain enhanced mobility, invasiveness, and survival abilities. However, the involvement of the EMT process in metastasis has been challenged by the finding that metastatic lesions showed similar epithelial phenotype as the primary tumors. Recent studies have suggested that a reversed process, mesenchymal to epithelial transition (MET) occurs during metastasis formation. By using an EMT/MET tracking system, we plan to determine the involvement of the EMT/MET process in lung cancer metastasis and explore the necessity of these processes for metastasis formation in animal models. The outcome of the proposed studies will improve our understanding of lung cancer metastasis and provide mechanism insights that may contribute to the development of more efficient therapeutic approaches in combating the deadly disease. |
