China Oncology ›› 2019, Vol. 29 ›› Issue (9): 681-687.doi: 10.19401/j.cnki.1007-3639.2019.09.001

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The effects of Runx2 on TGF-β1-induced epithelial-mesenchymal transition in lung cancer A549 cells

GENG Wenwen, PU Qian, GAO Haidong   

  1. Department of General Surgery, Qilu Hospital of Shandong University (Qingdao), Qingdao 266000, Shandong Province, China
  • Online:2019-09-30 Published:2019-11-20
  • Contact: GAO Haidong E-mail: haidonggao@sdu.edu.cn

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