High-throughput systems to dissect Snail-driven malignancy
Initial Award Abstract
Molecular details regarding the factors that regulate the early development of lung cancer and its early spread to other sites are currently incomplete. Epithelial-Mesenchymal Transition (EMT) is a process critical during early tissue development when cells lose cell-to-cell contacts (epithelial state) and acquire properties that cause cells to migrate and invade other tissues (mesenchymal state).
An increasing number of studies suggest that EMT would facilitate the early steps of carcinogenesis and metastasis. Several studies also support the idea that this tumor spread can occur at very early stages of cancer growth, perhaps even when the tumor is initially formed. A protein called Snail/SNAI1 is a key EMT regulator and its up-regulation has been associated with early formation of cancer, cancer progression, and early tumor spread.
The overall objective of the proposed research is to discover targets of clinical use for the detection, prevention and treatment of early cancer formation that is caused by Snail. To this aim, we propose an extensive study of the activity of the protein Snail in early lung cancer formation and early dissemination utilizing large-scale experiments that can detect when Snail is inhibited and loses its effect. Our previous work demonstrates that this study can be carried out successfully.
We think that Snail stability can be targeted to disrupt the formation of lung cancer and its spread to other sites. We anticipate that this extensive study will lead to the identification of a list of factors that inhibit cell movement caused by Snail, and this could be exploited clinically for the early detection of lung cancer and the prevention of its spread to other sites.