Cargando…
c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1
The c-Jun N-terminal protein kinases (JNKs) JNK1 and JNK2 can act as either tumor suppressors or pro-oncogenic kinases in human cancers. The isoform-specific roles for JNK1 and JNK2 in human pancreatic cancer are still unclear, the question which should be addressed in this project. Human pancreatic...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761571/ https://www.ncbi.nlm.nih.gov/pubmed/33526844 http://dx.doi.org/10.1038/s41417-020-00290-5 |
_version_ | 1784633559322984448 |
---|---|
author | Tian, Xiaodong Traub, Benno Shi, Jingwei Huber, Nadine Schreiner, Stefan Chen, Guowei Zhou, Shaoxia Henne-Bruns, Doris Knippschild, Uwe Kornmann, Marko |
author_facet | Tian, Xiaodong Traub, Benno Shi, Jingwei Huber, Nadine Schreiner, Stefan Chen, Guowei Zhou, Shaoxia Henne-Bruns, Doris Knippschild, Uwe Kornmann, Marko |
author_sort | Tian, Xiaodong |
collection | PubMed |
description | The c-Jun N-terminal protein kinases (JNKs) JNK1 and JNK2 can act as either tumor suppressors or pro-oncogenic kinases in human cancers. The isoform-specific roles for JNK1 and JNK2 in human pancreatic cancer are still unclear, the question which should be addressed in this project. Human pancreatic cancer cell lines MIA PaCa-2 and PANC-1 clones were established either expressing either JNK1 or -2 shRNA in a stable manner. Basal anchorage-dependent and –independent cell growth, single-cell movement, and invasion using the Boyden chamber assay were analyzed. Xenograft growth was assessed using an orthotopic mouse model. All seven tested pancreatic cancer cell lines expressed JNKs as did human pancreatic cancer samples determined by immunohistochemistry. Pharmacological, unspecific JNK inhibition (SP600125) reduced cell growth of all cell lines but PANC-1. Especially inhibition of JNK2 resulted in overall increased oncogenic potential with increased proliferation and invasion, associated with alterations in cytoskeleton structure. Specific inhibition of JNK1 revealed opposing functions. Overall, JNK1 and JNK2 can exert different functions in human pancreatic cancer and act as counter players for tumor invasion. Specifically modulating the activity of JNKs may be of potential therapeutic interest in the future. |
format | Online Article Text |
id | pubmed-8761571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-87615712022-01-26 c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 Tian, Xiaodong Traub, Benno Shi, Jingwei Huber, Nadine Schreiner, Stefan Chen, Guowei Zhou, Shaoxia Henne-Bruns, Doris Knippschild, Uwe Kornmann, Marko Cancer Gene Ther Article The c-Jun N-terminal protein kinases (JNKs) JNK1 and JNK2 can act as either tumor suppressors or pro-oncogenic kinases in human cancers. The isoform-specific roles for JNK1 and JNK2 in human pancreatic cancer are still unclear, the question which should be addressed in this project. Human pancreatic cancer cell lines MIA PaCa-2 and PANC-1 clones were established either expressing either JNK1 or -2 shRNA in a stable manner. Basal anchorage-dependent and –independent cell growth, single-cell movement, and invasion using the Boyden chamber assay were analyzed. Xenograft growth was assessed using an orthotopic mouse model. All seven tested pancreatic cancer cell lines expressed JNKs as did human pancreatic cancer samples determined by immunohistochemistry. Pharmacological, unspecific JNK inhibition (SP600125) reduced cell growth of all cell lines but PANC-1. Especially inhibition of JNK2 resulted in overall increased oncogenic potential with increased proliferation and invasion, associated with alterations in cytoskeleton structure. Specific inhibition of JNK1 revealed opposing functions. Overall, JNK1 and JNK2 can exert different functions in human pancreatic cancer and act as counter players for tumor invasion. Specifically modulating the activity of JNKs may be of potential therapeutic interest in the future. Nature Publishing Group US 2021-02-01 2022 /pmc/articles/PMC8761571/ /pubmed/33526844 http://dx.doi.org/10.1038/s41417-020-00290-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tian, Xiaodong Traub, Benno Shi, Jingwei Huber, Nadine Schreiner, Stefan Chen, Guowei Zhou, Shaoxia Henne-Bruns, Doris Knippschild, Uwe Kornmann, Marko c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title | c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title_full | c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title_fullStr | c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title_full_unstemmed | c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title_short | c-Jun N-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-Jun N-terminal kinase 1 |
title_sort | c-jun n-terminal kinase 2 suppresses pancreatic cancer growth and invasion and is opposed by c-jun n-terminal kinase 1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761571/ https://www.ncbi.nlm.nih.gov/pubmed/33526844 http://dx.doi.org/10.1038/s41417-020-00290-5 |
work_keys_str_mv | AT tianxiaodong cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT traubbenno cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT shijingwei cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT hubernadine cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT schreinerstefan cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT chenguowei cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT zhoushaoxia cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT hennebrunsdoris cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT knippschilduwe cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 AT kornmannmarko cjunnterminalkinase2suppressespancreaticcancergrowthandinvasionandisopposedbycjunnterminalkinase1 |