BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor

• Published in: Cancer letters 2016-10, Vol.381 (2), p.314-322
• Main Authors: Park, Seong Ji, Choi, Yu Sun, Lee, Seungkoo, Lee, Young Jae, Hong, Suntaek, Han, Sanghwa, Kim, Byung-Chul
• Format: Article
• Language: English
• Subjects: A549 Cells; Adenosine Triphosphate - metabolism; Aniline Compounds - metabolism; Aniline Compounds - pharmacology; Animals; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Binding Sites; BIX02189; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - secondary; Cell Movement - drug effects; Dose-Response Relationship, Drug; EMT; Epithelial-Mesenchymal Transition - drug effects; Female; Hematology, Oncology and Palliative Medicine; Humans; Indoles - metabolism; Indoles - pharmacology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; MAP Kinase Kinase 5 - antagonists & inhibitors; MAP Kinase Kinase 5 - genetics; MAP Kinase Kinase 5 - metabolism; Mice, Inbred BALB C; Mice, Nude; Mitogen-Activated Protein Kinase 7 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 7 - genetics; Mitogen-Activated Protein Kinase 7 - metabolism; Molecular Docking Simulation; Neoplasm Invasiveness; Protein Binding; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; Receptors, Transforming Growth Factor beta - metabolism; RNA Interference; Signal Transduction - drug effects; Smad Proteins - metabolism; TGF-β1; Transfection; Transforming Growth Factor beta1 - pharmacology; TβRI; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2016.08.010

Highlights • BIX02189 inhibits TGF-β1-induced EMT and cell migration in A549 lung cancer cells. • The inhibitory effect of BIX02189 is independent of its action as a MEK5 inhibitor. • BIX02189 directly binds to TβRI and suppresses its kinase activity. • BIX02189 blocks the metastatic spread of A549 cells in a xenograft mouse model. • BIX02189 may have use as a potential therapeutic agent for human lung cancer.