| First Author | Park CY | Year | 2014 |
| Journal | Cancer Lett | Volume | 351 |
| Issue | 1 | Pages | 72-80 |
| PubMed ID | 24887560 | Mgi Jnum | J:213497 |
| Mgi Id | MGI:5585204 | Doi | 10.1016/j.canlet.2014.05.006 |
| Citation | Park CY, et al. (2014) An novel inhibitor of TGF-beta type I receptor, IN-1130, blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition. Cancer Lett 351(1):72-80 |
| abstractText | TGF-beta signaling plays an important role in breast cancer progression and metastasis. Epithelial-mesenchymal transition (EMT) is an important step in the progression of solid tumors to metastatic disease. We previously reported that IN-1130, a novel transforming growth factor-beta type I receptor kinase (ALK5) inhibitor, suppressed renal fibrosis in obstructive nephropathy (Moon et al., 2006). Here, we show that IN-1130 suppressed EMT and the lung metastasis of mammary tumors in mouse models. Treating human and mouse cell lines with IN-1130 inhibited TGF-beta-mediated transcriptional activation, the phosphorylation and nuclear translocation of Smad2, and TGF-beta-induced-EMT, which induces morphological changes in epithelial cells. Additionally, we demonstrated that IN-1130 blocked TGF-beta-induced 4T1 mammary cancer cell migration and invasion. The TGF-beta-mediated increase in matrix metalloproteinase (MMP)-2 and MMP-9 expression was restored by IN-1130 co-treatment with TGF-beta in human epithelial cells and in 4T1 cells. Furthermore, we found that lung metastasis from primary breast cancer was inhibited by IN-1130 in both 4T1-xenografted BALB/c mice and MMTV/c-Neu transgenic mice without any change in primary tumor volume. IN-1130 prolonged the life span of tumor-bearing mice. In summary, this study indicated that IN-1130 has therapeutic potential for preventing breast cancer metastasis to the lung. |
