For example, insulin-like growth factor-1 (IGF-1) increases the migration of CS cells by increasing αvβ1 integrin expression54, and CXCL12/SDF-1 chemokine, which is normally secreted by the lung epithelium, enhances the invasiveness of CS cells by increasing αvβ3 integrin expression through the CXCR4/ERK/NF-κB pathway55. This evidence concerns the gene CXCL12 and Cowden syndrome 1.