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Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway
INTRODUCTION: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705283/ https://www.ncbi.nlm.nih.gov/pubmed/33273827 http://dx.doi.org/10.2147/OTT.S284219 |
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author | Su, Xingxing Yang, Yishi Ma, Le Luo, Peng Shen, Kaicheng Dai, Haisu Jiang, Yan Shuai, Ling Liu, Zhipeng You, Jinshan Min, Ke Shi, Chunmeng Chen, Zhiyu |
author_facet | Su, Xingxing Yang, Yishi Ma, Le Luo, Peng Shen, Kaicheng Dai, Haisu Jiang, Yan Shuai, Ling Liu, Zhipeng You, Jinshan Min, Ke Shi, Chunmeng Chen, Zhiyu |
author_sort | Su, Xingxing |
collection | PubMed |
description | INTRODUCTION: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors. However, no studies investigated the potential role of PC4 in PDAC. METHODS: We investigated PC4 expression in 81 PDAC tissue samples using immunohistochemistry and studied the impact of PC4 expression and the molecular mechanisms of this altered expression on PDAC tumorigenesis and proliferation both in vitro and in vivo. RESULTS: PC4 overexpression was correlated with a poor outcome in PDAC patients. The RNAi-mediated knockdown of PC4 expression in CFPAC-1 and AsPC-1 cell lines reduced cell proliferation and tumor growth. The loss of PC4 in PDAC inhibits cell growth by inducing cell cycle arrest at the G1/S transition and suppressing the mTOR/p70s6k pathway. DISCUSSION/CONCLUSION: Our findings reveal for the first time that PC4 exerts oncogenic functions by activating mTOR/p70s6k signaling pathway-mediated cell proliferation, implying that PC4 is a promising therapeutic target for PDAC. |
format | Online Article Text |
id | pubmed-7705283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-77052832020-12-02 Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway Su, Xingxing Yang, Yishi Ma, Le Luo, Peng Shen, Kaicheng Dai, Haisu Jiang, Yan Shuai, Ling Liu, Zhipeng You, Jinshan Min, Ke Shi, Chunmeng Chen, Zhiyu Onco Targets Ther Original Research INTRODUCTION: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors. However, no studies investigated the potential role of PC4 in PDAC. METHODS: We investigated PC4 expression in 81 PDAC tissue samples using immunohistochemistry and studied the impact of PC4 expression and the molecular mechanisms of this altered expression on PDAC tumorigenesis and proliferation both in vitro and in vivo. RESULTS: PC4 overexpression was correlated with a poor outcome in PDAC patients. The RNAi-mediated knockdown of PC4 expression in CFPAC-1 and AsPC-1 cell lines reduced cell proliferation and tumor growth. The loss of PC4 in PDAC inhibits cell growth by inducing cell cycle arrest at the G1/S transition and suppressing the mTOR/p70s6k pathway. DISCUSSION/CONCLUSION: Our findings reveal for the first time that PC4 exerts oncogenic functions by activating mTOR/p70s6k signaling pathway-mediated cell proliferation, implying that PC4 is a promising therapeutic target for PDAC. Dove 2020-11-26 /pmc/articles/PMC7705283/ /pubmed/33273827 http://dx.doi.org/10.2147/OTT.S284219 Text en © 2020 Su et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Su, Xingxing Yang, Yishi Ma, Le Luo, Peng Shen, Kaicheng Dai, Haisu Jiang, Yan Shuai, Ling Liu, Zhipeng You, Jinshan Min, Ke Shi, Chunmeng Chen, Zhiyu Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title | Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title_full | Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title_fullStr | Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title_full_unstemmed | Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title_short | Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway |
title_sort | human positive coactivator 4 affects the progression and prognosis of pancreatic ductal adenocarcinoma via the mtor/p70s6k signaling pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705283/ https://www.ncbi.nlm.nih.gov/pubmed/33273827 http://dx.doi.org/10.2147/OTT.S284219 |
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