Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating beta-catenin/TCF pathway.
Esophageal squamous cell carcinoma (ESCC) has a multifactorial etiology involving environmental and/or genetic factors. End-binding protein 1 (EB1), which was cloned as an interacting partner of the adenomatous polyposis coli (APC) tumor suppressor protein, was previously found overexpressed in ESCC. However, the precise role of EB1 in the development of this malignancy has not yet been elucidated. In this study, we analysed freshly resected ESCC specimens and demonstrated that EB1 was overexpressed in approximately 63% of tumor samples compared to matched normal tissue. We report that overexpression of EB1 in the ESCC line EC9706 significantly promotes cell growth, whereas suppression of EB1 protein level by RNA interference significantly inhibited growth of esophageal tumor cells. In addition, EB1 overexpression induced nuclear accumulation of beta-catenin and promoted the transcriptional activity of beta-catenin/T-cell factor (TCF). These effects were partially or completely abolished by coexpression of APC or DeltaN TCF4, respectively. Also, we found that EB1 affected the interaction between beta-catenin and APC. Furthermore, EB1 overexpression was correlated with cytoplasmic/nuclear accumulation of beta-catenin in primary human ESCC. Taken together, these results support the novel hypothesis that EB1 overexpression may play a role in the development of ESCC by affecting APC function and activating the beta-catenin/TCF pathway.
Wang
Yihua
Y
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing.
Zhou
Xiaobo
X
Zhu
Hongxia
H
Liu
Shuang
S
Zhou
Cuiqi
C
Zhang
Guo
G
Xue
Liyan
L
Lu
Ning
N
Quan
Lanping
L
Bai
Jinfeng
J
Zhan
Qimin
Q
Xu
Ningzhi
N
D001483:Base Sequence; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D015534:Trans-Activators; D051176:beta Catenin