WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer
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 pro...
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Molecular Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12943-017-0693-9 |
| _version_ | 1818256718500462592 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shuai Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T17:32:13Z |
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| id | doaj.art-f52adfa4f9d9443ead3124b5fde75862 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-12T17:32:13Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-f52adfa4f9d9443ead3124b5fde758622022-12-22T00:17:20ZengBMCMolecular Cancer1476-45982017-07-011611910.1186/s12943-017-0693-9WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancerShuai Chen0Han Wang1Yu-Fan Huang2Ming-Li Li3Jiang-Hong Cheng4Peng Hu5Chuan-Hui Lu6Ya Zhang7Na Liu8Chi-Meng Tzeng9Zhi-Ming Zhang10Department of Breast Surgery, The First Affiliated Hospital of Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xiamen UniversityTranslational Medicine Research Center (TMRC), School of Pharmaceutical Science, Xiamen UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xiamen UniversityAbstract 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.http://link.springer.com/article/10.1186/s12943-017-0693-9WW domainWBP2Breast cancerEstrogen receptorSignaling pathwayTyrosine kinase |
| spellingShingle | 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 WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer Molecular Cancer WW domain WBP2 Breast cancer Estrogen receptor Signaling pathway Tyrosine kinase |
| title | WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer |
| title_full | WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer |
| title_fullStr | WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer |
| title_full_unstemmed | WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer |
| title_short | WW domain-binding protein 2: an adaptor protein closely linked to the development of breast cancer |
| title_sort | ww domain binding protein 2 an adaptor protein closely linked to the development of breast cancer |
| topic | WW domain WBP2 Breast cancer Estrogen receptor Signaling pathway Tyrosine kinase |
| url | http://link.springer.com/article/10.1186/s12943-017-0693-9 |
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