Roles of ezrin in the growth and invasiveness of esophageal squamous carcinoma cells.
Ezrin, which crosslinks the cytoskeleton and plasma membrane, is involved in the growth and metastatic potential of cancer cells. Ezrin expression in esophageal squamous cell carcinoma (ESCC) was described recently, but its roles and the underlying mechanism(s) remain unclear. In our study, we first showed that ezrin in ESCC cell is expressed in the nucleus as well as in the cytoplasm and plasma membrane. Then, by using RNAi, we revealed that interference of ezrin expression suppressed the growth, adhesion and invasiveness of ESCC cells. Tumorigenesis experiments revealed that ezrin may directly regulate tumor formation in vivo. To explore the molecular mechanisms through which ezrin contributes to the proliferation and invasiveness of ESCC cells, we used cDNA microarrays to analyze ezrin knockdown cells and the control cells; of 39,000 genes examined, 297 were differentially expressed upon ezrin knockdown, including some proliferation- and invasiveness-related genes such as ATF3, CTGF and CYR61. Furthermore, pathway analysis showed that ezrin knockdown led to decreased activation of the TGF-beta and MAPK pathways, and ezrin-mediated cell invasiveness alteration was dependent on the activation of these pathways. Finally, immunohistochemical staining on 80 ESCC specimens and 50 normal esophageal mucosae revealed that the expression levels of 3 altered genes involved in the regulation of cell proliferation and tumor metastasis, including CTGF, CYR61 and ATF3, were altered in ESCCs, and their expression pattern correlated with ezrin expression. Taken together, we propose that ezrin might function in the growth and invasiveness of ESCC cells through the MAPK and TGF-beta pathways.
Xie
Jian-Jun
JJ
Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, People's Republic of China.
Xu
Li-Yan
LY
Xie
Yang-Min
YM
Zhang
Hai-Hua
HH
Cai
Wei-Jia
WJ
Zhou
Fei
F
Shen
Zhong-Ying
ZY
Li
En-Min
EM
D051700:Activating Transcription Factor 3 / Q000235:genetics; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D000099149:Ezrin
D051700:Activating Transcription Factor 3; D055513:Connective Tissue Growth Factor; D055515:Cysteine-Rich Protein 61; D003598:Cytoskeletal Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D000099149:Ezrin; C490449:ATF3 protein, human; C501848:CCN1 protein, human; C526317:CCN2 protein, human