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

Molecular Cancer

Review

Chuan-Hui Lu¹  Yu-Fan Huang¹  Na Liu¹  Zhi-Ming Zhang²  Shuai Chen³  Ming-Li Li⁴  Ya Zhang⁴  Jiang-Hong Cheng⁴  Han Wang⁴  Peng Hu⁵  Chi-Meng Tzeng⁵ 

[1]Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[2]Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[3]Teaching Hospital of Fujian Medical University, 350004, Fuzhou, Fujian, People’s Republic of China

[4]Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[5]Translational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[6]Key Laboratory for Cancer T-Cell Therapeutics and Clinical Translation (CTCTCT), 361005, Xiamen, Fujian, People’s Republic of China

[7]Translational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[8]Key Laboratory for Cancer T-Cell Therapeutics and Clinical Translation (CTCTCT), 361005, Xiamen, Fujian, People’s Republic of China

[9]Translational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen University, 361005, Xiamen, Fujian, People’s Republic of China

[10]Key Laboratory for Cancer T-Cell Therapeutics and Clinical Translation (CTCTCT), 361005, Xiamen, Fujian, People’s Republic of China

[11]INNOVA Cell Theranostics/Clinics and TRANSLA Health Group, Yangzhou, Jiangsu, People’s Republic of China

关键词: WW domain;    WBP2;    Breast cancer;    Estrogen receptor;    Signaling pathway;    Tyrosine kinase;   

DOI  :  10.1186/s12943-017-0693-9

 received in 2016-12-16, accepted in 2017-07-10,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017