Wnt信号通路
生物
癌变
癌症研究
结直肠癌
大肠癌小鼠模型的建立
癌症
细胞周期
连环蛋白
信号转导
连环素
基因沉默
细胞生长
细胞生物学
遗传学
基因
作者
Bin Wang,Yuanxin Liang,Xingxing Chai,Shasha Chen,Ziyu Ye,Ronggang Li,Xiaoping Li,Gang Kong,Yanyun Li,Xueying Zhang,Zhengping Che,Yong‐Ke You,Shicai Ye,Lili Li,Bihua Lin,Juan Huang,Mingyuan Huang,Xin Zhang,Xianxiu Qiu,Jincheng Zeng
标识
DOI:10.1016/j.yexcr.2020.112170
摘要
Colorectal cancer is the second leading cause of cancer mortality worldwide with poor prognosis and high recurrence. Aberrant Wnt/β-catenin signaling promotes oncogenesis by transcriptional activation of c-Myc and its downstream signals. EDAR is characterized as an important effector of canonical Wnt signaling in developing skin appendages, but the interplay between EDAR and Wnt signaling in tumorigenesis and progression remains to be elucidated. In this study, we revealed that EDAR expression is prevalently elevated in colorectal cancer tissues compared with normal tissues. Further analysis suggests there is a strict correlation between EDAR expression and colorectal cancer progression. EDAR silencing by shRNA in colorectal cancer cells showed proliferative suppression via retarding cell cycle at G1 phase. Xenograft mice transplanted with shEDAR-transduced tumor cells significantly alleviated tumor burden in comparison with control mice. Furthermore, downregulation of EDAR was accompanied by reduction of β-catenin, c-Myc and other G1 cell cycle regulators, while β-catenin agonist restored the expression of these proteins and overrode the proliferative block induced by EDAR knockdown. These findings indicate that EDAR functions as a component of Wnt/β-catenin signaling pathway, and is a potential modulator in colorectal carcinogenesis.
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