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Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is a disease with an extremely poor prognosis that is characterized by a rich extracellular matrix (ECM). Tenascin-C (TNC) is a component of the ECM and plays a role in tumour progression. In this study, we reported that TNC is overexpressed in PDAC tissues an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277647/ https://www.ncbi.nlm.nih.gov/pubmed/30519351 http://dx.doi.org/10.7150/jca.25926 |
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author | Cai, Jun Lu, Wenli Du, Shaoxia Guo, Zhongkui Wang, Hui Wei, Wei Shen, Xiaohong |
author_facet | Cai, Jun Lu, Wenli Du, Shaoxia Guo, Zhongkui Wang, Hui Wei, Wei Shen, Xiaohong |
author_sort | Cai, Jun |
collection | PubMed |
description | Pancreatic ductal adenocarcinoma (PDAC) is a disease with an extremely poor prognosis that is characterized by a rich extracellular matrix (ECM). Tenascin-C (TNC) is a component of the ECM and plays a role in tumour progression. In this study, we reported that TNC is overexpressed in PDAC tissues and is correlated with tumour stage and cyclin D1 expression. Cyclin D1 is key regulator of the cell cycle G1/S transition. Further experiments revealed that TNC promotes G1/S transition through AKT signalling. TNC/AKT increases the expression of cyclin D1 by enhancing the transcriptional activity of β-catenin, whereas the translocation of FOXO1 from the nucleus results in the downregulation of p27(Kip1). Cyclin D1 and p27(Kip1) regulate the activity of cyclin D1-CDK4 complexes and retinoblastoma (Rb), and then they stimulate the progression of G1/S transition and tumour cell proliferation. In conclusion, TNC exerts its activating effect on the proliferation of pancreatic cancer cells in vitro and in vivo through its functional target AKT/FOXO1/β-catenin. The molecular mechanisms that drive PDAC progression will be useful for the development of molecular markers and the evaluation of patient prognosis. |
format | Online Article Text |
id | pubmed-6277647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-62776472018-12-05 Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer Cai, Jun Lu, Wenli Du, Shaoxia Guo, Zhongkui Wang, Hui Wei, Wei Shen, Xiaohong J Cancer Research Paper Pancreatic ductal adenocarcinoma (PDAC) is a disease with an extremely poor prognosis that is characterized by a rich extracellular matrix (ECM). Tenascin-C (TNC) is a component of the ECM and plays a role in tumour progression. In this study, we reported that TNC is overexpressed in PDAC tissues and is correlated with tumour stage and cyclin D1 expression. Cyclin D1 is key regulator of the cell cycle G1/S transition. Further experiments revealed that TNC promotes G1/S transition through AKT signalling. TNC/AKT increases the expression of cyclin D1 by enhancing the transcriptional activity of β-catenin, whereas the translocation of FOXO1 from the nucleus results in the downregulation of p27(Kip1). Cyclin D1 and p27(Kip1) regulate the activity of cyclin D1-CDK4 complexes and retinoblastoma (Rb), and then they stimulate the progression of G1/S transition and tumour cell proliferation. In conclusion, TNC exerts its activating effect on the proliferation of pancreatic cancer cells in vitro and in vivo through its functional target AKT/FOXO1/β-catenin. The molecular mechanisms that drive PDAC progression will be useful for the development of molecular markers and the evaluation of patient prognosis. Ivyspring International Publisher 2018-10-31 /pmc/articles/PMC6277647/ /pubmed/30519351 http://dx.doi.org/10.7150/jca.25926 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Cai, Jun Lu, Wenli Du, Shaoxia Guo, Zhongkui Wang, Hui Wei, Wei Shen, Xiaohong Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title | Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title_full | Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title_fullStr | Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title_full_unstemmed | Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title_short | Tenascin-C Modulates Cell Cycle Progression to Enhance Tumour Cell Proliferation through AKT/FOXO1 Signalling in Pancreatic Cancer |
title_sort | tenascin-c modulates cell cycle progression to enhance tumour cell proliferation through akt/foxo1 signalling in pancreatic cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277647/ https://www.ncbi.nlm.nih.gov/pubmed/30519351 http://dx.doi.org/10.7150/jca.25926 |
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