Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells
The Hippo signaling cascade is frequently dysregulated in a variety of cancers, such as breast cancer (BC), which is one of the most commonly diagnosed malignancies in women. Among BC subtypes, triple-negative BC (TNBC) stands out due to its poor prognosis and high metastatic potential. Despite exte...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Chemosensors |
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| Online Access: | https://www.mdpi.com/2227-9040/11/9/492 |
| _version_ | 1797580821636317184 |
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| author | Liqing Wu Anni Ge Yawei Hao Xiaolong Yang |
| author_facet | Liqing Wu Anni Ge Yawei Hao Xiaolong Yang |
| author_sort | Liqing Wu |
| collection | DOAJ |
| description | The Hippo signaling cascade is frequently dysregulated in a variety of cancers, such as breast cancer (BC), which is one of the most commonly diagnosed malignancies in women. Among BC subtypes, triple-negative BC (TNBC) stands out due to its poor prognosis and high metastatic potential. Despite extensive research aimed at establishing treatment options, existing therapies demonstrate limited efficacy for TNBC. Recently, it has been recognized that targeting the core components of the Hippo pathway (YAP and its paralog TAZ) is a promising strategy for developing anti-cancer treatment. However, no YAP/TAZ inhibitors have been approved by the FDA as anti-TNBC treatments, and only a few compounds have been identified that directly affect YAP and TAZ activity and stability to enhance the prospect of innovative HiBiT biosensors for monitoring of YAP and TAZ in cells. Employing these biosensors, we conducted a small-scale drug screen involving 279 compounds, leading to the identification of several small molecule inhibitors (SMIs) capable of inducing YAP/TAZ degradation in diverse TNBC cell lines. It is worth noting that some drugs may indirectly affect the protein stability following prolonged treatment, and a shorter exposure can be included in the future to identify drug candidates with more direct effects. Nevertheless, our study introduces a novel approach for assessing YAP and TAZ levels, which can have significant implications for developing anti-TNBC targeted therapies. |
| first_indexed | 2024-03-10T22:55:26Z |
| format | Article |
| id | doaj.art-9c20670c55f246c38d8f975b4931fa3e |
| institution | Directory Open Access Journal |
| issn | 2227-9040 |
| language | English |
| last_indexed | 2024-03-10T22:55:26Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Chemosensors |
| spelling | doaj.art-9c20670c55f246c38d8f975b4931fa3e2023-11-19T10:02:07ZengMDPI AGChemosensors2227-90402023-09-0111949210.3390/chemosensors11090492Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in CellsLiqing Wu0Anni Ge1Yawei Hao2Xiaolong Yang3Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, CanadaDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, CanadaDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, CanadaDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, CanadaThe Hippo signaling cascade is frequently dysregulated in a variety of cancers, such as breast cancer (BC), which is one of the most commonly diagnosed malignancies in women. Among BC subtypes, triple-negative BC (TNBC) stands out due to its poor prognosis and high metastatic potential. Despite extensive research aimed at establishing treatment options, existing therapies demonstrate limited efficacy for TNBC. Recently, it has been recognized that targeting the core components of the Hippo pathway (YAP and its paralog TAZ) is a promising strategy for developing anti-cancer treatment. However, no YAP/TAZ inhibitors have been approved by the FDA as anti-TNBC treatments, and only a few compounds have been identified that directly affect YAP and TAZ activity and stability to enhance the prospect of innovative HiBiT biosensors for monitoring of YAP and TAZ in cells. Employing these biosensors, we conducted a small-scale drug screen involving 279 compounds, leading to the identification of several small molecule inhibitors (SMIs) capable of inducing YAP/TAZ degradation in diverse TNBC cell lines. It is worth noting that some drugs may indirectly affect the protein stability following prolonged treatment, and a shorter exposure can be included in the future to identify drug candidates with more direct effects. Nevertheless, our study introduces a novel approach for assessing YAP and TAZ levels, which can have significant implications for developing anti-TNBC targeted therapies.https://www.mdpi.com/2227-9040/11/9/492HiBiTbiosensorYAP/TAZtriple-negative breast cancer |
| spellingShingle | Liqing Wu Anni Ge Yawei Hao Xiaolong Yang Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells Chemosensors HiBiT biosensor YAP/TAZ triple-negative breast cancer |
| title | Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells |
| title_full | Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells |
| title_fullStr | Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells |
| title_full_unstemmed | Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells |
| title_short | Development of a New HiBiT Biosensor Monitoring Stability of YAP/TAZ Proteins in Cells |
| title_sort | development of a new hibit biosensor monitoring stability of yap taz proteins in cells |
| topic | HiBiT biosensor YAP/TAZ triple-negative breast cancer |
| url | https://www.mdpi.com/2227-9040/11/9/492 |
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