title: Overexpression of transferrin receptor CD71 and its tumorigenic properties in esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is the predominant type of esophageal cancer in endemic Asian regions. In the present study, we investigated the clinical implication and role of transferrin receptor CD71 in ESCC. CD71 has a physiological role in cellular iron intake and is implicated in the carcinogenesis of various types of tumors. In our cohort, more than a 2-fold upregulation of the CD71 transcript was detected in 61.5% of patients using quantitative polymerase chain reaction. Immunohistochemical analysis also showed strong membranous and cytoplasmic localization of CD71 in paraffin-embedded tumors. Staining parallel tumor sections with the proliferative marker Ki-67 revealed that the pattern of Ki-67 staining was associated with CD71 expression. Analysis of clinicopathological data indicated that CD71 overexpression can be used as an indicator for advanced T4 stage (p=0.0307). These data suggested a strong link between CD71 and ESCC. Subsequent in vitro assays using short interfering RNA (siRNA) to suppress CD71 expression confirmed the tumorigenic properties of CD71 in ESCC; cell growth inhibition and cell cycle arrest at S phase were observed in CD71-suppressed cells. The underlying mechanism involved activation of the MEK/ERK pathway. In summary, the present study provides evidence showing the tumorigenic properties of CD71 in ESCC with clinical correlations and suggests targeting CD71 as a strategy for the treatment of ESCC.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Kin Tak
authors.initials: KT
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Mei Yuk
authors.initials: MY
authors.lastname: Choi
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Kenneth K Y
authors.initials: KK
authors.lastname: Lai
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Winnie
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Lai Nar
authors.initials: LN
authors.lastname: Tung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Ho Yu
authors.initials: HY
authors.lastname: Lam
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Daniel K H
authors.initials: DK
authors.lastname: Tong
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Simon
authors.initials: S
authors.lastname: Law
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034741:RNA, Small Interfering / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin