Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782467211155210240 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5107595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT choiyiseul her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT koyoungsan her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT parkjinju her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT choiyoungsun her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT kimyounghoon her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT pyojungsoo her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT jangbogun her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT hwangdoukho her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT kimwooho her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer AT leebyunglan her2inducedmetastasisismediatedbyaktjnkemtsignalingpathwayingastriccancer |