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Transcription factor AP‐2β suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner β‐catenin
Author(s) -
Wang Fangmei,
Huang Wenhuan,
Hu Xiang,
Chen Cheng,
Li Xinxin,
Qiu Junlu,
Liang Zhongheng,
Zhang Jianmei,
Li Limin,
Wang Xiaoqing,
Ding Xiaofeng,
Xiang Shuanglin,
Zhang Jian
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22646
Subject(s) - biology , wnt signaling pathway , transcription factor , catenin , carcinogenesis , cell growth , immunoprecipitation , microbiology and biotechnology , cell culture , cancer research , signal transduction , gene , genetics
Transcription factor AP‐2β mediates the transcription of a number of genes implicated in mammalian development, cell proliferation, and carcinogenesis. Although the expression pattern of AP‐2β has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP‐2β are unknown. Here, we found that AP‐2β significantly inhibits TCF/LEF reporter activity. Moreover, AP‐2β and β‐catenin interact both in vitro through GST pull‐down assays and in vivo by co‐immunoprecipitation. We further identified the interaction regions to the DNA‐binding domain of AP‐2β and the 1‐9 Armadillo repeats of β‐catenin. Moreover, AP‐2β binds with β‐TrCP and promotes the degradation of endogenous β‐catenin via the proteasomal degradation pathway. Immunohistochemistry analysis revealed a negative correlation between the two proteins in cervical cancer tissues and cell lines. Finally, functional analysis showed that AP‐2β suppresses cervical cancer cell growth in vitro and in vivo by inhibiting the expression of Wnt downstream genes. Taken together, these findings demonstrated that AP‐2β functions as a novel inhibitor of the Wnt/β‐catenin signaling pathway in cervical cancer.