关键词: 上皮-间质转化, 肿瘤, 转化生长因子-&beta, Runx2

Abstract: Background and purpose: Transforming growth factor-β (TGF-β) signaling has been shown to play an important role in epithelial-mesenchymal transition (EMT). Furthermore, Runx2 plays an important role in the progress of tumor metastasis and is also regulated by TGF-β signaling. This study was designed to investigate the induction of EMT in response to TGF-β and the role of Runx2 in this process. Methods: A549 cells (donated by Tianjin Medical University Cancer Institute and Hospital) were induced by TGF-β1 to build the EMT model. The cells were infected with siRNA to downregulate the expression of Runx2. Phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway were blocked by specific inhibitor LY294002 and PD98059 to explore the mechanism. Results: The EMT model was induced by 5 ng/mL TGF-β1 for 72 h. At the same time, downregulation of Runx2 with siRNA could prevent cancer cell from the progress of EMT. In addition, the results showed PI3K/AKT-MAPK/ERK and TGF-β signaling pathways were both activated in this process, and the expression of Runx2 was significantly decreased after blocking PI3K/AKT pathway, compared with the MAPK/ERK pathway. Conclusion: TGF-β1 regulates Runx2 to affect the progression of EMT mainly by the PI3K/AKT pathway, and Runx2 plays a necessary role in the process of tumor cell EMT.

Key words:  Epithelial-mesenchymal transition, Neoplasms, Transforming growth factor-β, Runx2