TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway
The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.613869/full |
| _version_ | 1818945054519066624 |
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| author | Xi Yu Shenglan Li Mingrui Pang Yang Du Tao Xu Tao Bai Kang Yang Juncheng Hu Shaoming Zhu Lei Wang Xiuheng Liu |
| author_facet | Xi Yu Shenglan Li Mingrui Pang Yang Du Tao Xu Tao Bai Kang Yang Juncheng Hu Shaoming Zhu Lei Wang Xiuheng Liu |
| author_sort | Xi Yu |
| collection | DOAJ |
| description | The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment. |
| first_indexed | 2024-12-20T07:53:01Z |
| format | Article |
| id | doaj.art-d3b77783896641c3a8043e9eeee2bcb0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T07:53:01Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-d3b77783896641c3a8043e9eeee2bcb02022-12-21T19:47:47ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.613869613869TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT PathwayXi Yu0Shenglan Li1Mingrui Pang2Yang Du3Tao Xu4Tao Bai5Kang Yang6Juncheng Hu7Shaoming Zhu8Lei Wang9Xiuheng Liu10Department of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Radiography, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, ChinaThe tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.https://www.frontiersin.org/articles/10.3389/fonc.2020.613869/fullcell cycleapoptosisPI3K/AKTPTENbladder cancerTSPAN7 |
| spellingShingle | Xi Yu Shenglan Li Mingrui Pang Yang Du Tao Xu Tao Bai Kang Yang Juncheng Hu Shaoming Zhu Lei Wang Xiuheng Liu TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway Frontiers in Oncology cell cycle apoptosis PI3K/AKT PTEN bladder cancer TSPAN7 |
| title | TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway |
| title_full | TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway |
| title_fullStr | TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway |
| title_full_unstemmed | TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway |
| title_short | TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway |
| title_sort | tspan7 exerts anti tumor effects in bladder cancer through the pten pi3k akt pathway |
| topic | cell cycle apoptosis PI3K/AKT PTEN bladder cancer TSPAN7 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.613869/full |
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