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Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT
In many cancer types, integrin-mediated signaling regulates proliferation, survival and invasion of tumorigenic cells. However, it is still unclear how integrins crosstalk with oncogenes to regulate tumorigenesis and metastasis. Here we show that oncogenic K-Ras(V12) upregulates α6-integrin expressi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658677/ https://www.ncbi.nlm.nih.gov/pubmed/28604746 http://dx.doi.org/10.1038/onc.2017.177 |
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author | Zhang, K Myllymäki, S-M Gao, P Devarajan, R Kytölä, V Nykter, M Wei, G-H Manninen, A |
author_facet | Zhang, K Myllymäki, S-M Gao, P Devarajan, R Kytölä, V Nykter, M Wei, G-H Manninen, A |
author_sort | Zhang, K |
collection | PubMed |
description | In many cancer types, integrin-mediated signaling regulates proliferation, survival and invasion of tumorigenic cells. However, it is still unclear how integrins crosstalk with oncogenes to regulate tumorigenesis and metastasis. Here we show that oncogenic K-Ras(V12) upregulates α6-integrin expression in Madin–Darby canine kidney (MDCK) cells via activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)/Fos-related antigen 1-signaling cascade. Activated α6-integrins promoted metastatic capacity and anoikis resistance, and led to perturbed growth of MDCK cysts. Transcriptomic analysis of K-Ras(V12)-transformed MDCK cells also revealed robust downregulation of αV-class integrins. Re-expression of αV-integrin in K-Ras(V12)-transformed MDCK cells synergistically upregulated the expression of Zinc finger E-box-binding homeobox 1 and Twist-related protein 1 and triggered epithelial-mesenchymal transition leading to induced cell motility and invasion. These results delineate the signaling cascades connecting oncogenic K-Ras(V12) with α6- and αV-integrin functions to modulate cancer cell survival and tumorigenesis, and reveal new possible strategies to target highly oncogenic K-Ras(V12) mutants. |
format | Online Article Text |
id | pubmed-5658677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-56586772017-10-30 Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT Zhang, K Myllymäki, S-M Gao, P Devarajan, R Kytölä, V Nykter, M Wei, G-H Manninen, A Oncogene Original Article In many cancer types, integrin-mediated signaling regulates proliferation, survival and invasion of tumorigenic cells. However, it is still unclear how integrins crosstalk with oncogenes to regulate tumorigenesis and metastasis. Here we show that oncogenic K-Ras(V12) upregulates α6-integrin expression in Madin–Darby canine kidney (MDCK) cells via activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)/Fos-related antigen 1-signaling cascade. Activated α6-integrins promoted metastatic capacity and anoikis resistance, and led to perturbed growth of MDCK cysts. Transcriptomic analysis of K-Ras(V12)-transformed MDCK cells also revealed robust downregulation of αV-class integrins. Re-expression of αV-integrin in K-Ras(V12)-transformed MDCK cells synergistically upregulated the expression of Zinc finger E-box-binding homeobox 1 and Twist-related protein 1 and triggered epithelial-mesenchymal transition leading to induced cell motility and invasion. These results delineate the signaling cascades connecting oncogenic K-Ras(V12) with α6- and αV-integrin functions to modulate cancer cell survival and tumorigenesis, and reveal new possible strategies to target highly oncogenic K-Ras(V12) mutants. Nature Publishing Group 2017-10-12 2017-06-12 /pmc/articles/PMC5658677/ /pubmed/28604746 http://dx.doi.org/10.1038/onc.2017.177 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ 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/ |
spellingShingle | Original Article Zhang, K Myllymäki, S-M Gao, P Devarajan, R Kytölä, V Nykter, M Wei, G-H Manninen, A Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title | Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title_full | Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title_fullStr | Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title_full_unstemmed | Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title_short | Oncogenic K-Ras upregulates ITGA6 expression via FOSL1 to induce anoikis resistance and synergizes with αV-Class integrins to promote EMT |
title_sort | oncogenic k-ras upregulates itga6 expression via fosl1 to induce anoikis resistance and synergizes with αv-class integrins to promote emt |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658677/ https://www.ncbi.nlm.nih.gov/pubmed/28604746 http://dx.doi.org/10.1038/onc.2017.177 |
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