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Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and their loss has been correlated with poor prognosis in human cancer. Mutational activation of protein kinases and loss of cell adhesion occur together in human lung adenocarcinoma but how these two...

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Detalles Bibliográficos
Autor principal: Götz, Rudolf
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427011/
https://www.ncbi.nlm.nih.gov/pubmed/18492263
http://dx.doi.org/10.1186/1475-2867-8-7
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author Götz, Rudolf
author_facet Götz, Rudolf
author_sort Götz, Rudolf
collection PubMed
description Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and their loss has been correlated with poor prognosis in human cancer. Mutational activation of protein kinases and loss of cell adhesion occur together in human lung adenocarcinoma but how these two pathways interconnect is only poorly understood. Mouse models of human lung adenocarcinoma with oncogene expression targeted to subtypes of lung epithelial cells led to formation of adenomas or adenocarcinomas that lacked metastatic potential. Conditional genetic abrogation of epithelial tumour cell adhesion in mice with benign lung tumours induced by oncogenic RAF kinase has been demonstrated to induce intratumourous vascularization (angiogenic switch), progression to invasive adenocarcinoma and micrometastasis. Importantly, breaking cell adhesion in benign oncogene-driven lung tumour cells activated β-catenin signalling and induced the expression of several genes that are normally expressed in intestine rather than the lung. I will discuss potential routes to nuclear β-catenin signalling in cancer and how nuclear β-catenin may epigenetically alter the plasticity of tumour cells during malignant progression.
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spelling pubmed-24270112008-06-13 Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression Götz, Rudolf Cancer Cell Int Review Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and their loss has been correlated with poor prognosis in human cancer. Mutational activation of protein kinases and loss of cell adhesion occur together in human lung adenocarcinoma but how these two pathways interconnect is only poorly understood. Mouse models of human lung adenocarcinoma with oncogene expression targeted to subtypes of lung epithelial cells led to formation of adenomas or adenocarcinomas that lacked metastatic potential. Conditional genetic abrogation of epithelial tumour cell adhesion in mice with benign lung tumours induced by oncogenic RAF kinase has been demonstrated to induce intratumourous vascularization (angiogenic switch), progression to invasive adenocarcinoma and micrometastasis. Importantly, breaking cell adhesion in benign oncogene-driven lung tumour cells activated β-catenin signalling and induced the expression of several genes that are normally expressed in intestine rather than the lung. I will discuss potential routes to nuclear β-catenin signalling in cancer and how nuclear β-catenin may epigenetically alter the plasticity of tumour cells during malignant progression. BioMed Central 2008-05-20 /pmc/articles/PMC2427011/ /pubmed/18492263 http://dx.doi.org/10.1186/1475-2867-8-7 Text en Copyright © 2008 Götz; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Götz, Rudolf
Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title_full Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title_fullStr Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title_full_unstemmed Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title_short Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
title_sort inter-cellular adhesion disruption and the ras/raf and beta-catenin signalling in lung cancer progression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427011/
https://www.ncbi.nlm.nih.gov/pubmed/18492263
http://dx.doi.org/10.1186/1475-2867-8-7
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