克洛丹
MAPK/ERK通路
癌症研究
细胞生长
表皮生长因子
生物
癌基因
信号转导
细胞外
表皮生长因子受体
细胞培养
癌症
紧密连接
细胞生物学
细胞周期
遗传学
作者
Kumi Takasawa,Akira Takasawa,Makoto Osanai,Tomoyuki Aoyama,Yoshio Ono,Tsuyoshi Kono,Yoshihiko Hirohashi,Masaki Murata,Norimasa Sawada
标识
DOI:10.1016/j.canlet.2017.05.033
摘要
Our recent work revealed that elevated expression of claudin-18 is involved in bile duct neoplasia. In the present study, we found that wound generation of a cell sheet de novo induced claudin-18 expression in its leading edge, coincident with high mitotic activity. We also found that the suppression of claudin-18 expression significantly reduced cell growth and invasiveness of bile duct cancer cell lines and tumorigenicity in vivo. In addition, an antibody specific to an extracellular loop of claudin-18 showed similar effects on the cells such as cell proliferation. Interestingly, treatment with epidermal growth factor (EGF) and overexpression of RAS oncogene induced claudin-18 expression by activation of extracellular signal-related kinase (ERK)1/2. Furthermore, enhanced claudin-18 expression activated ERK1/2. These findings provide evidence for an oncogenic property of claudin-18 in bile duct carcinoma cells via modulation of EGFR/ERK signaling, indicating that claudin-18 is a possible therapeutic target for this malignancy.
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