PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition
PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer pat...
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| Format: | Article |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.536072/full |
| _version_ | 1819275490303672320 |
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| author | Zhongyu Wang Jun Shang Zhiqin Li Huanhuan Li Chufan Zhang Kai He Shikang Li Wen Ju |
| author_facet | Zhongyu Wang Jun Shang Zhiqin Li Huanhuan Li Chufan Zhang Kai He Shikang Li Wen Ju |
| author_sort | Zhongyu Wang |
| collection | DOAJ |
| description | PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT. |
| first_indexed | 2024-12-23T23:25:09Z |
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| id | doaj.art-fc22fcac558d4811a7d19895be2c74d9 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-23T23:25:09Z |
| publishDate | 2020-12-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-fc22fcac558d4811a7d19895be2c74d92022-12-21T17:26:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-12-011010.3389/fonc.2020.536072536072PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal TransitionZhongyu Wang0Jun Shang1Zhiqin Li2Huanhuan Li3Chufan Zhang4Kai He5Shikang Li6Wen Ju7Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.https://www.frontiersin.org/articles/10.3389/fonc.2020.536072/fullPIK3CACUX1EMTprognosisbladder cancer |
| spellingShingle | Zhongyu Wang Jun Shang Zhiqin Li Huanhuan Li Chufan Zhang Kai He Shikang Li Wen Ju PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition Frontiers in Oncology PIK3CA CUX1 EMT prognosis bladder cancer |
| title | PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition |
| title_full | PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition |
| title_fullStr | PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition |
| title_full_unstemmed | PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition |
| title_short | PIK3CA Is Regulated by CUX1, Promotes Cell Growth and Metastasis in Bladder Cancer via Activating Epithelial-Mesenchymal Transition |
| title_sort | pik3ca is regulated by cux1 promotes cell growth and metastasis in bladder cancer via activating epithelial mesenchymal transition |
| topic | PIK3CA CUX1 EMT prognosis bladder cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.536072/full |
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