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Mol Carcinog. 2017 Aug;56(8):1909-1923. doi: 10.1002/mc.22646. Epub 2017 Apr 11.

Transcription factor AP-2β suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner β-catenin.

Author information

1
Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Changsha, Hunan, China.
2
Reproductive Medicine Center, Changsha Hospital for Maternal & Child Health Care, Changsha, Hunan, China.
3
College of Engineering and Design, Hunan Normal University, Changsha, Hunan, China.
4
Xiangya Second Hospital, Central South University, Changsha, Hunan, China.

Abstract

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.

KEYWORDS:

AP-2β; cervical cancer; β-catenin

PMID:
28277615
DOI:
10.1002/mc.22646
[Indexed for MEDLINE]

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