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Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism c...

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Autores principales: Lee, Tsai-Yu, Liu, Chia-Lin, Chang, Yun-Ching, Nieh, Shin, Lin, Yaoh-Shiang, Jao, Shu-Wen, Chen, Su-Feng, Liu, Tsung-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029643/
https://www.ncbi.nlm.nih.gov/pubmed/26992205
http://dx.doi.org/10.18632/oncotarget.8049
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author Lee, Tsai-Yu
Liu, Chia-Lin
Chang, Yun-Ching
Nieh, Shin
Lin, Yaoh-Shiang
Jao, Shu-Wen
Chen, Su-Feng
Liu, Tsung-Yun
author_facet Lee, Tsai-Yu
Liu, Chia-Lin
Chang, Yun-Ching
Nieh, Shin
Lin, Yaoh-Shiang
Jao, Shu-Wen
Chen, Su-Feng
Liu, Tsung-Yun
author_sort Lee, Tsai-Yu
collection PubMed
description A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC.
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spelling pubmed-50296432016-09-29 Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative Lee, Tsai-Yu Liu, Chia-Lin Chang, Yun-Ching Nieh, Shin Lin, Yaoh-Shiang Jao, Shu-Wen Chen, Su-Feng Liu, Tsung-Yun Oncotarget Research Paper A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC. Impact Journals LLC 2016-03-14 /pmc/articles/PMC5029643/ /pubmed/26992205 http://dx.doi.org/10.18632/oncotarget.8049 Text en Copyright: © 2016 Lee et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lee, Tsai-Yu
Liu, Chia-Lin
Chang, Yun-Ching
Nieh, Shin
Lin, Yaoh-Shiang
Jao, Shu-Wen
Chen, Su-Feng
Liu, Tsung-Yun
Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title_full Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title_fullStr Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title_full_unstemmed Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title_short Increased chemoresistance via Snail–Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
title_sort increased chemoresistance via snail–raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029643/
https://www.ncbi.nlm.nih.gov/pubmed/26992205
http://dx.doi.org/10.18632/oncotarget.8049
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