Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progres- sion; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-inde- pendent growth, cell migration and invasion in KRAS gene mutant cells but to a les- ser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high- level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene sig- nature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.
- Colorectal Cancer
- Connectivity mapping
Wei, R., Wong, J. P. C., Lyu, P., Xi, X., Tong, O. L. H., Zhang, S-D., Yuen, HF., Shirasawa, S., & Kwok, H. F. (2018). In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer. Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/jcmm.13686