Proteomic Analysis of Colorectal Cancer Metastasis: Stathmin-1 Revealed as a Player in Cancer Cell Migration and Prognostic Marker
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- 作者：Hwee Tong Tan ; Wei Wu ; Yi Zhen Ng ; Xuxiao Zhang ; Benedict Yan ; Chee Wee Ong ; Sandra Tan ; Manuel Salto-Tellez ; Shing Chuan Hooi ; Maxey C. M. Chung
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：February 3, 2012
- 年：2012
- 卷：11
- 期：2
- 页码：1433-1445
- 全文大小：834K
- 年卷期：v.11,no.2(February 3, 2012)
- ISSN：1535-3907
文摘
Metastasis accounts largely for the high mortality rate of colorectal cancer (CRC) patients. In this study, we performed comparative proteome analysis of primary CRC cell lines HCT-116 and its metastatic derivative E1 using 2-D DIGE. We identified 74 differentially expressed proteins, many of which function in transcription, translation, angiogenesis signal transduction, or cytoskeletal remodeling pathways, which are indispensable cellular processes involved in the metastatic cascade. Among these proteins, stathmin-1 (STMN1) was found to be highly up-regulated in E1 as compared to HCT-116 and was thus selected for further functional studies. Our results showed that perturbations in STMN1 levels resulted in significant changes in cell migration, invasion, adhesion, and colony formation. We further showed that the differential expression of STMN1 correlated with the cells鈥?metastatic potential in other paradigms of CRC models. Using immunohistochemistry, we also showed that STMN1 was highly expressed in colorectal primary tumors and metastatic tissues as compared to the adjacent normal colorectal tissues. Furthermore, we also showed via tissue microarray analyses of 324 CRC tissues and Kaplan鈥揗eier survival plot that CRC patients with higher expression of STMN1 have poorer prognosis.