서강대학교

초록/요약

Role of transforming growth factor beta (TGF-β) in cancer has been controversial due to its growth inhibitory as well as tumor promoting effect. Mostly, Epithelial mesenchymal transition (EMT) induced by TGF-β has been considered to be one of major event for tumor invasion and metastasis. Since pharmaceutical approach to inhibit cancer invasion and consequent metastasis has been suggested to be a promising novel anti-cancer therapy, it would be critical to understand the molecular mechanisms underlying EMT and successive acquisition of invasive properties in cancers. In these studies, I identified the integrin β3 (ITGB3) in a non-small cell lung carcinoma (NSCLC) cell line (A549) as a target molecule of TGF-β. Loss of ITGB3 significantly impaired the migration capacity of A549 cells. Of interest, ITGB3 expression was suppressed in cell density dependent manner, suggesting that dissimilating cancer cells detached from the primary tumor would be actively migrated due to expression of ITGB3. I also found that SMAD family member 4 (SMAD4), serving as a key transcription factor along with SMAD2 and SMAD3 underwent nuclear translocation concurrently with transcriptional coactivator with PDZ-binding motif (TAZ), at low cell density. These data suggest that TAZ and SMAD4 interaction is responsible for SMAD4 dependent ITGB3 expression, which may account for acquisition of migration capability of dissimilating cancer cells. Such interesting research hypothesis remains further profound study. Given that ITGB3 expression in NSCLC revealed the poor prognosis, ITGB3 or a molecule(s) governing ITGB3 expression (e.g. SMAD4 or TAZ) would be a potential target for a novel anti-metastatic therapy in future.