title: CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo.
abstract: CD10 expression was identified as a contributor to cancer progression in several cancers; however, the exact biological significance and mechanism of CD10 expression remains unclear. In addition, CD10 expression in esophageal squamous cell carcinoma (ESCC) has not been studied. We investigated the relationship between CD10 and Twist1. Furthermore, we examined the effect of CD10 on tumorigenicity using in vivo and in vitro systems as well as establishing the clinical significance of CD10 expression in ESCC using large clinical samples. CD10 expression was upregulated by Twist1 and there was a strong correlation between mRNA and protein expression. Twist1 can specifically upregulate CD10 at the transcriptional level via an interaction with the promoter region of CD10 and the proximal E-box CAGGTG in the CD10 promoter was identified as a binding site for Twist1. CD10 is frequently expressed in ESCC cell lines and silencing CD10 suppresses migration/invasion and anchorage-independent tumor growth of ESCC cells. Knockdown of CD10 inhibits the growth of ESCC xenograft in nude mice, suggesting that CD10 plays a role in enhancing the tumorigenesis of ESCC. From among 153 ESCC samples, 46 (30.0%) showed varying degrees of CD10 expression in cancer cells. In addition, stromal fibroblasts also showed varying amounts of CD10 expression in 92 (60.9%) tumor samples. CD10 overexpression in cancer cells as well as in stromal fibroblasts was an independent poor prognostic factor in both overall survival and disease-free survival. CD10 could be a promising target for the treatment of ESCC.
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Keun-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Chang Ohk
authors.initials: CO
authors.lastname: Sung
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Kang
authors.forename: Hae-Yong
authors.initials: HY
authors.lastname: Yoo
authors.forename: Hyeon-Ho
authors.initials: HH
authors.lastname: Kim
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Um
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016297:Mutagenesis, Site-Directed; D009367:Neoplasm Staging; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D015260:Neprilysin
keywords: CD10; MME; Twist1; carcinoma; esophagus; prognosis; stromal cell