Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis.
Esophagin/SPRR3 is one of the cornified-envelope structural precursor proteins, which is expressed during epithelia cell differentiation. In 1996, another research group discovered, and our own laboratory subsequently confirmed, frequent and dramatic decreased Esophagin/SPRR3 expression in esophageal squamous cell carcinoma (ESCC). However, the role of Esophagin/SPRR3 in tumorigenesis of esophageal epithelium remains undetermined. In this study, we demonstrate that expression of Esophagin/SPRR3 is frequently downregulated in ESCC. In contrast, no correlations between downregulation of Esophagin/SPRR3 expression and clinicopathologic characteristics were observed. Diminished Esophagin/SPRR3 expression was present in dysplastic epithelia, suggesting that Esophagin/SPRR3 alteration could represent an early event in squamous carcinogenesis of the esophagus. Exogenous expression of Esophagin/SPRR3 significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar, as well as tumor formation in vivo. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end label assay and immunofluorescence analysis of the active form of Caspase 3 indicated that dysregulated apoptosis might contribute to reduced tumorigenicity. In particular, upregulation of CDK11p46 protein was observed in ESCC cells expressing Esophagin/SPRR3, but not in control cells, indicating that Esophagin/SPRR3-induced apoptosis may be due, at least in part, to increased expression of CDK11p46 protein. These findings suggest that Esophagin/SPRR3 may play a role in the maintenance of normal esophageal epithelial homeostasis, and that aberrant expression of Esophagin/SPRR3 may contribute to the tumorigenesis of ESCC.
Zhang
Yu
Y
State Key Laboratory of Molecular Oncology, Cancer Institute Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Feng
Yan-Bin
YB
Shen
Xiao-Ming
XM
Chen
Bao-Sheng
BS
Du
Xiao-Li
XL
Luo
Man-Li
ML
Cai
Yan
Y
Han
Ya-Ling
YL
Xu
Xin
X
Zhan
Qi-Min
QM
Wang
Ming-Rong
MR
D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011487:Protein Conformation