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Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling

Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatm...

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Autores principales: Xu, Bao-Qing, Fu, Zhi-Guang, Meng, Yao, Wu, Xiao-Qing, Wu, Bo, Xu, Liang, Jiang, Jian-Li, Li, Ling, Chen, Zhi-Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308719/
https://www.ncbi.nlm.nih.gov/pubmed/27556697
http://dx.doi.org/10.18632/oncotarget.11405
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author Xu, Bao-Qing
Fu, Zhi-Guang
Meng, Yao
Wu, Xiao-Qing
Wu, Bo
Xu, Liang
Jiang, Jian-Li
Li, Ling
Chen, Zhi-Nan
author_facet Xu, Bao-Qing
Fu, Zhi-Guang
Meng, Yao
Wu, Xiao-Qing
Wu, Bo
Xu, Liang
Jiang, Jian-Li
Li, Ling
Chen, Zhi-Nan
author_sort Xu, Bao-Qing
collection PubMed
description Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer.
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spelling pubmed-53087192017-03-09 Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling Xu, Bao-Qing Fu, Zhi-Guang Meng, Yao Wu, Xiao-Qing Wu, Bo Xu, Liang Jiang, Jian-Li Li, Ling Chen, Zhi-Nan Oncotarget Research Paper Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer. Impact Journals LLC 2016-08-19 /pmc/articles/PMC5308719/ /pubmed/27556697 http://dx.doi.org/10.18632/oncotarget.11405 Text en Copyright: © 2016 Xu 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
Xu, Bao-Qing
Fu, Zhi-Guang
Meng, Yao
Wu, Xiao-Qing
Wu, Bo
Xu, Liang
Jiang, Jian-Li
Li, Ling
Chen, Zhi-Nan
Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title_full Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title_fullStr Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title_full_unstemmed Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title_short Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling
title_sort gemcitabine enhances cell invasion via activating hab18g/cd147-egfr-pstat3 signaling
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308719/
https://www.ncbi.nlm.nih.gov/pubmed/27556697
http://dx.doi.org/10.18632/oncotarget.11405
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