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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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Autores principales: Yu, Xi, Li, Shenglan, Pang, Mingrui, Du, Yang, Xu, Tao, Bai, Tao, Yang, Kang, Hu, Juncheng, Zhu, Shaoming, Wang, Lei, Liu, Xiuheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821430/
https://www.ncbi.nlm.nih.gov/pubmed/33489923
http://dx.doi.org/10.3389/fonc.2020.613869
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author Yu, Xi
Li, Shenglan
Pang, Mingrui
Du, Yang
Xu, Tao
Bai, Tao
Yang, Kang
Hu, Juncheng
Zhu, Shaoming
Wang, Lei
Liu, Xiuheng
author_facet Yu, Xi
Li, Shenglan
Pang, Mingrui
Du, Yang
Xu, Tao
Bai, Tao
Yang, Kang
Hu, Juncheng
Zhu, Shaoming
Wang, Lei
Liu, Xiuheng
author_sort Yu, Xi
collection PubMed
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.
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spelling pubmed-78214302021-01-23 TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway Yu, Xi Li, Shenglan Pang, Mingrui Du, Yang Xu, Tao Bai, Tao Yang, Kang Hu, Juncheng Zhu, Shaoming Wang, Lei Liu, Xiuheng Front Oncol Oncology 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. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7821430/ /pubmed/33489923 http://dx.doi.org/10.3389/fonc.2020.613869 Text en Copyright © 2021 Yu, Li, Pang, Du, Xu, Bai, Yang, Hu, Zhu, Wang and Liu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yu, Xi
Li, Shenglan
Pang, Mingrui
Du, Yang
Xu, Tao
Bai, Tao
Yang, Kang
Hu, Juncheng
Zhu, Shaoming
Wang, Lei
Liu, Xiuheng
TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway
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 Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821430/
https://www.ncbi.nlm.nih.gov/pubmed/33489923
http://dx.doi.org/10.3389/fonc.2020.613869
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