In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer.

Autor: Wei R; Faculty of Health Sciences, University of Macau, Taipa, Macau., Wong JPC; Faculty of Health Sciences, University of Macau, Taipa, Macau., Lyu P; Faculty of Health Sciences, University of Macau, Taipa, Macau., Xi X; Faculty of Health Sciences, University of Macau, Taipa, Macau., Tong O; Faculty of Health Sciences, University of Macau, Taipa, Macau., Zhang SD; Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, Londonderry, UK., Yuen HF; Institute of Molecular and Cell Biology, A*STAR, Singapore City, Singapore., Shirasawa S; Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan., Kwok HF; Faculty of Health Sciences, University of Macau, Taipa, Macau.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2018 Sep; Vol. 22 (9), pp. 4097-4105. Date of Electronic Publication: 2018 May 30.
DOI: 10.1111/jcmm.13686
Abstrakt: Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser 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 signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.
(© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
Databáze: MEDLINE
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