title: Proteomic analysis of colorectal cancer metastasis: stathmin-1 revealed as a player in cancer cell migration and prognostic marker.
abstract: 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' 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-Meier survival plot that CRC patients with higher expression of STMN1 have poorer prognosis.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , 8 Medical Drive, Singapore 117597, Singapore.
authors.forename: Hwee Tong
authors.initials: HT
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yi Zhen
authors.initials: YZ
authors.lastname: Ng
authors.forename: Xuxiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Benedict
authors.initials: B
authors.lastname: Yan
authors.forename: Chee Wee
authors.initials: CW
authors.lastname: Ong
authors.forename: Sandra
authors.initials: S
authors.lastname: Tan
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Shing Chuan
authors.initials: SC
authors.lastname: Hooi
authors.forename: Maxey C M
authors.initials: MC
authors.lastname: Chung
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D011379:Prognosis; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D050777:Stathmin / Q000032:analysis* / Q000378:metabolism; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; C493995:STMN1 protein, human; D050777:Stathmin