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HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer

AIM: To investigated the relationships between HER2, c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2-positive gastric cancer (GC) cells. METHODS: Immunohistochemistry was performed on tissue array slides containing 423 human GC specimens. Using H...

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Autores principales: Choi, Yiseul, Ko, Young San, Park, Jinju, Choi, Youngsun, Kim, Younghoon, Pyo, Jung-Soo, Jang, Bo Gun, Hwang, Douk Ho, Kim, Woo Ho, Lee, Byung Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107595/
https://www.ncbi.nlm.nih.gov/pubmed/27895401
http://dx.doi.org/10.3748/wjg.v22.i41.9141
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author Choi, Yiseul
Ko, Young San
Park, Jinju
Choi, Youngsun
Kim, Younghoon
Pyo, Jung-Soo
Jang, Bo Gun
Hwang, Douk Ho
Kim, Woo Ho
Lee, Byung Lan
author_facet Choi, Yiseul
Ko, Young San
Park, Jinju
Choi, Youngsun
Kim, Younghoon
Pyo, Jung-Soo
Jang, Bo Gun
Hwang, Douk Ho
Kim, Woo Ho
Lee, Byung Lan
author_sort Choi, Yiseul
collection PubMed
description AIM: To investigated the relationships between HER2, c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2-positive gastric cancer (GC) cells. METHODS: Immunohistochemistry was performed on tissue array slides containing 423 human GC specimens. Using HER2-positve GC cell lines SNU-216 and NCI-N87, HER2 expression was silenced by RNA interference, and the activations of JNK and AKT were suppressed by SP600125 and LY294002, respectively. Transwell assay, Western blot, semi-quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were used in cell culture experiments. RESULTS: In GC specimens, HER2, JNK, and AKT activations were positively correlated with each other. In vitro analysis revealed a positive regulatory feedback loop between HER2 and JNK in GC cell lines and the role of JNK as a downstream effector of AKT in the HER2/AKT signaling pathway. JNK inhibition suppressed migratory capacity through reversing EMT and dual inhibition of JNK and AKT induced a more profound effect on cancer cell motility. CONCLUSION: HER2, JNK and AKT in human GC specimens are positively associated with each other. JNK and AKT, downstream effectors of HER2, co-operatively contribute to the metastatic potential of HER2-positive GC cells. Thus, targeting of these two molecules in combination with HER2 downregulation may be a good approach to combat HER2-positive GC.
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spelling pubmed-51075952016-11-28 HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer Choi, Yiseul Ko, Young San Park, Jinju Choi, Youngsun Kim, Younghoon Pyo, Jung-Soo Jang, Bo Gun Hwang, Douk Ho Kim, Woo Ho Lee, Byung Lan World J Gastroenterol Basic Study AIM: To investigated the relationships between HER2, c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2-positive gastric cancer (GC) cells. METHODS: Immunohistochemistry was performed on tissue array slides containing 423 human GC specimens. Using HER2-positve GC cell lines SNU-216 and NCI-N87, HER2 expression was silenced by RNA interference, and the activations of JNK and AKT were suppressed by SP600125 and LY294002, respectively. Transwell assay, Western blot, semi-quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were used in cell culture experiments. RESULTS: In GC specimens, HER2, JNK, and AKT activations were positively correlated with each other. In vitro analysis revealed a positive regulatory feedback loop between HER2 and JNK in GC cell lines and the role of JNK as a downstream effector of AKT in the HER2/AKT signaling pathway. JNK inhibition suppressed migratory capacity through reversing EMT and dual inhibition of JNK and AKT induced a more profound effect on cancer cell motility. CONCLUSION: HER2, JNK and AKT in human GC specimens are positively associated with each other. JNK and AKT, downstream effectors of HER2, co-operatively contribute to the metastatic potential of HER2-positive GC cells. Thus, targeting of these two molecules in combination with HER2 downregulation may be a good approach to combat HER2-positive GC. Baishideng Publishing Group Inc 2016-11-07 2016-11-07 /pmc/articles/PMC5107595/ /pubmed/27895401 http://dx.doi.org/10.3748/wjg.v22.i41.9141 Text en ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Choi, Yiseul
Ko, Young San
Park, Jinju
Choi, Youngsun
Kim, Younghoon
Pyo, Jung-Soo
Jang, Bo Gun
Hwang, Douk Ho
Kim, Woo Ho
Lee, Byung Lan
HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title_full HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title_fullStr HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title_full_unstemmed HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title_short HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
title_sort her2-induced metastasis is mediated by akt/jnk/emt signaling pathway in gastric cancer
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107595/
https://www.ncbi.nlm.nih.gov/pubmed/27895401
http://dx.doi.org/10.3748/wjg.v22.i41.9141
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