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Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ
Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial‐mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high‐glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521329/ https://www.ncbi.nlm.nih.gov/pubmed/32678516 http://dx.doi.org/10.1111/jcmm.15653 |
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author | Li, Shi Zhu, Hua Chen, Hongde Xia, Jianling Zhang, Fangyi Xu, Ruoting Lin, Qi |
author_facet | Li, Shi Zhu, Hua Chen, Hongde Xia, Jianling Zhang, Fangyi Xu, Ruoting Lin, Qi |
author_sort | Li, Shi |
collection | PubMed |
description | Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial‐mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high‐glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC‐3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT‐associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High‐glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high‐glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D. |
format | Online Article Text |
id | pubmed-7521329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75213292020-10-02 Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ Li, Shi Zhu, Hua Chen, Hongde Xia, Jianling Zhang, Fangyi Xu, Ruoting Lin, Qi J Cell Mol Med Original Articles Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial‐mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high‐glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC‐3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT‐associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High‐glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high‐glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D. John Wiley and Sons Inc. 2020-07-17 2020-09 /pmc/articles/PMC7521329/ /pubmed/32678516 http://dx.doi.org/10.1111/jcmm.15653 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Li, Shi Zhu, Hua Chen, Hongde Xia, Jianling Zhang, Fangyi Xu, Ruoting Lin, Qi Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title | Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title_full | Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title_fullStr | Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title_full_unstemmed | Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title_short | Glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ |
title_sort | glucose promotes epithelial‐mesenchymal transitions in bladder cancer by regulating the functions of yap1 and taz |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521329/ https://www.ncbi.nlm.nih.gov/pubmed/32678516 http://dx.doi.org/10.1111/jcmm.15653 |
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