Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/53175 |
Resumo: | © 2015 Macmillan Publishers Limited All rights reserved. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0 |
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Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation© 2015 Macmillan Publishers Limited All rights reserved. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0This study was designed to evaluate MEK5 and ERK5 expression in colon cancer progression and to ascertain the relevance of MEK5/ERK5 signalling in colon cancer. Expression of MEK5 and ERK5 was evaluated in 323 human colon cancer samples. To evaluate the role of MEK5/ERK5 signalling in colon cancer, we developed a stable cell line model with differential MEK5/ERK5 activation. Impact of differential MEK5/ERK5 signalling was evaluated on cell cycle progression by flow cytometry and cell migration was evaluated by wound healing and transwell migration assays. Finally, we used an orthotopic xenograft mouse model of colon cancer to assess tumour growth and progression. Our results demonstrated that MEK5 and ERK5 are overexpressed in human adenomas (P<0.01) and adenocarcinomas (P<0.05), where increased ERK5 expression correlated with the acquisition of more invasive and metastatic potential (P<0.05). Interestingly, we observed a significant correlation between ERK5 expression and NF-κB activation in human adenocarcinomas (P<0.001). We also showed that ERK5 overactivation significantly accelerated cell cycle progression (P<0.05) and increased cell migration (P<0.01). Furthermore, cells with overactivated ERK5 displayed increased NF-κB nuclear translocation and transcriptional activity (P<0.05), together with increased expression of the mesenchymal marker vimentin (P<0.05). We further demonstrated that increased NF-κB activation was associated with increased IκB phosphorylation and degradation (P<0.05). Finally, in the mouse model, lymph node metastasis was exclusively seen in orthotopically implanted tumours with overactivated MEK5/ERK5, and not in tumours with inhibited MEK5/ERK5. Our results suggested that MEK5/ERK5/NF-κB signalling pathway is important for tumour onset, progression and metastasis, possibly representing a novel relevant therapeutic target in colon cancer treatment.This study was supported by Fundação para a Ciência e Tecnologia (HMSP-ICT/0018/2011, SFRH/BD/96517/2013, SFRH/BD/88619/2012 and SFRH/BD/79356/2011).Springer NatureRepositório da Universidade de LisboaSimões, AndréPereira, D. M.Gomes, S. E.Brito, H.Carvalho, TâniaFrench, A.Castro, Rui E.Steer, C. J.Thibodeau, S. N.Rodrigues, Cecília M. P.Borralho, P. M.2022-05-25T15:28:04Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53175engCell Death Dis. 2015 Apr 9;6(4):e171810.1038/cddis.2015.832041-4889info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:58:50Zoai:repositorio.ul.pt:10451/53175Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:08.664241Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| title |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| spellingShingle |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation Simões, André |
| title_short |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| title_full |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| title_fullStr |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| title_full_unstemmed |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| title_sort |
Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation |
| author |
Simões, André |
| author_facet |
Simões, André Pereira, D. M. Gomes, S. E. Brito, H. Carvalho, Tânia French, A. Castro, Rui E. Steer, C. J. Thibodeau, S. N. Rodrigues, Cecília M. P. Borralho, P. M. |
| author_role |
author |
| author2 |
Pereira, D. M. Gomes, S. E. Brito, H. Carvalho, Tânia French, A. Castro, Rui E. Steer, C. J. Thibodeau, S. N. Rodrigues, Cecília M. P. Borralho, P. M. |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Simões, André Pereira, D. M. Gomes, S. E. Brito, H. Carvalho, Tânia French, A. Castro, Rui E. Steer, C. J. Thibodeau, S. N. Rodrigues, Cecília M. P. Borralho, P. M. |
| description |
© 2015 Macmillan Publishers Limited All rights reserved. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0 |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2022-05-25T15:28:04Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/53175 |
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http://hdl.handle.net/10451/53175 |
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eng |
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eng |
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Cell Death Dis. 2015 Apr 9;6(4):e1718 10.1038/cddis.2015.83 2041-4889 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Springer Nature |
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Springer Nature |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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RCAAP |
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RCAAP |
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