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Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Review

WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer

Authors: Shuai Chen, Han Wang, Yu-Fan Huang, Ming-Li Li, Jiang-Hong Cheng, Peng Hu, Chuan-Hui Lu, Ya Zhang, Na Liu, Chi-Meng Tzeng, Zhi-Ming Zhang

Published in: Molecular Cancer | Issue 1/2017

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Abstract

The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo. Studies have confirmed that phosphorylated form of WBP2 can move into nuclei and activate the transcription of estrogen receptor (ER) and progesterone receptor (PR), whose expression were the indicators of breast cancer development, indicating that WBP2 may participate in the progression of breast cancer. Both overexpression of WBP2 and activation of tyrosine phosphorylation upregulate the signal cascades in the cross-regulation of the Wnt and ER signaling pathways in breast cancer. Following the binding of WBP2 to the WW domain region of TAZ which can accelerate migration, invasion and is required for the transformed phenotypes of breast cancer cells, the transformation of epithelial to mesenchymal of MCF10A is activated, suggesting that WBP2 is a key player in regulating cell migration. When WBP2 binds with WWOX, a tumor suppressor, ER transactivation and tumor growth can be suppressed. Thus, WBP2 may serve as a molecular on/off switch that controls the crosstalk between E2, WWOX, Wnt, TAZ, and other oncogenic signaling pathways. This review interprets the relationship between WBP2 and breast cancer, and provides comprehensive views about the function of WBP2 in the regulation of the pathogenesis of breast cancer and endocrine therapy in breast cancer treatment.
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Metadata
Title
WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer
Authors
Shuai Chen
Han Wang
Yu-Fan Huang
Ming-Li Li
Jiang-Hong Cheng
Peng Hu
Chuan-Hui Lu
Ya Zhang
Na Liu
Chi-Meng Tzeng
Zhi-Ming Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0693-9

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