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YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways

BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) p...

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Autores principales: Chen, Qun, Yang, Chuang, Chen, Lei, Zhang, Jing-Jing, Ge, Wan-Li, Yuan, Hao, Meng, Ling-Dong, Huang, Xu-Min, Shen, Peng, Miao, Yi, Jiang, Kui-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888832/
https://www.ncbi.nlm.nih.gov/pubmed/31631174
http://dx.doi.org/10.1038/s41416-019-0604-5
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author Chen, Qun
Yang, Chuang
Chen, Lei
Zhang, Jing-Jing
Ge, Wan-Li
Yuan, Hao
Meng, Ling-Dong
Huang, Xu-Min
Shen, Peng
Miao, Yi
Jiang, Kui-Rong
author_facet Chen, Qun
Yang, Chuang
Chen, Lei
Zhang, Jing-Jing
Ge, Wan-Li
Yuan, Hao
Meng, Ling-Dong
Huang, Xu-Min
Shen, Peng
Miao, Yi
Jiang, Kui-Rong
author_sort Chen, Qun
collection PubMed
description BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. METHODS: In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. RESULTS: Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. CONCLUSION: Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.
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spelling pubmed-68888322019-12-04 YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways Chen, Qun Yang, Chuang Chen, Lei Zhang, Jing-Jing Ge, Wan-Li Yuan, Hao Meng, Ling-Dong Huang, Xu-Min Shen, Peng Miao, Yi Jiang, Kui-Rong Br J Cancer Article BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. METHODS: In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. RESULTS: Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. CONCLUSION: Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer. Nature Publishing Group UK 2019-10-21 2019-11-26 /pmc/articles/PMC6888832/ /pubmed/31631174 http://dx.doi.org/10.1038/s41416-019-0604-5 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Qun
Yang, Chuang
Chen, Lei
Zhang, Jing-Jing
Ge, Wan-Li
Yuan, Hao
Meng, Ling-Dong
Huang, Xu-Min
Shen, Peng
Miao, Yi
Jiang, Kui-Rong
YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title_full YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title_fullStr YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title_full_unstemmed YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title_short YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
title_sort yy1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/mapk and pi3k/akt pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888832/
https://www.ncbi.nlm.nih.gov/pubmed/31631174
http://dx.doi.org/10.1038/s41416-019-0604-5
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