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P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer

Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF s...

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Autores principales: Kato, Shinichiro, Yokoyama, Satoru, Hayakawa, Yoshihiro, Li, Luhui, Iwakami, Yusuke, Sakurai, Hiroaki, Saiki, Ikuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084657/
https://www.ncbi.nlm.nih.gov/pubmed/27403934
http://dx.doi.org/10.1111/cas.13009
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author Kato, Shinichiro
Yokoyama, Satoru
Hayakawa, Yoshihiro
Li, Luhui
Iwakami, Yusuke
Sakurai, Hiroaki
Saiki, Ikuo
author_facet Kato, Shinichiro
Yokoyama, Satoru
Hayakawa, Yoshihiro
Li, Luhui
Iwakami, Yusuke
Sakurai, Hiroaki
Saiki, Ikuo
author_sort Kato, Shinichiro
collection PubMed
description Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non‐small‐cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC‐14, A549, and PC‐9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF.
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spelling pubmed-50846572016-10-31 P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer Kato, Shinichiro Yokoyama, Satoru Hayakawa, Yoshihiro Li, Luhui Iwakami, Yusuke Sakurai, Hiroaki Saiki, Ikuo Cancer Sci Original Articles Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non‐small‐cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC‐14, A549, and PC‐9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. John Wiley and Sons Inc. 2016-09-01 2016-10 /pmc/articles/PMC5084657/ /pubmed/27403934 http://dx.doi.org/10.1111/cas.13009 Text en © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Kato, Shinichiro
Yokoyama, Satoru
Hayakawa, Yoshihiro
Li, Luhui
Iwakami, Yusuke
Sakurai, Hiroaki
Saiki, Ikuo
P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title_full P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title_fullStr P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title_full_unstemmed P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title_short P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
title_sort p38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non‐small‐cell lung cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084657/
https://www.ncbi.nlm.nih.gov/pubmed/27403934
http://dx.doi.org/10.1111/cas.13009
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