title: Twist mediates an aggressive phenotype in human colorectal cancer cells.
abstract: Epithelial-mesenchymal transition (EMT) is a crucial process providing cancer cells with the ability to migrate and metastasize to distant sites. Recently, EMT was shown to be associated with the cancer stem cell (CSC) phenotype and chemoresistance. Twist is a transcription factor that regulates EMT in a various cancer cells, including colorectal cancer (CRC). Our study was done to determine the role of Twist in mediating aggressive phenotype in CRC. Human CRC cell lines were transduced with a retroviral Twist construct or vector control. Migration and invasion abilities were determined in vitro using modified Boyden chamber assays. Mammosphere formation assay was performed to detect CSC characteristics. EMT and CSC markers were detected using western blotting and RT-PCR. Chemosensitivity to oxaliplatin of the transfected cells were determined by the MTT assay. Human CRC specimens were stained for Twist and P-gp expression. Twist overexpression triggered EMT and a CSC-like phenotype in human CRC cells and enhanced cell migration, invasion and mammosphere formation abilities. In addition, Twist-overexpressing CRC cells were more chemo-resistant to oxaliplatin than control cells. Furthermore, Twist over-expression increased P-gp expression in CRC cells, which is a transmembrane glycoprotein conferred multidrug-resistance phenotype to various cancer cells. Importantly, Twist and P-gp were expressed correlatively in human CRC specimens. Thus, Twist is a potential therapeutic target in metastatic CRC.
authors.affiliation: Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Tao
authors.affiliation: Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Ye
authors.affiliation: Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics*; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000737:chemistry; D000077150:Oxaliplatin; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D009687:Nuclear Proteins; D009944:Organoplatinum Compounds; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D000077150:Oxaliplatin