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Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer
BACKGROUND: Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777165/ https://www.ncbi.nlm.nih.gov/pubmed/23949920 http://dx.doi.org/10.1007/s13402-013-0143-7 |
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author | Vlug, Eva J. van de Ven, Robert A. H. Vermeulen, Jeroen F. Bult, Peter van Diest, Paul J. Derksen, Patrick W. B. |
author_facet | Vlug, Eva J. van de Ven, Robert A. H. Vermeulen, Jeroen F. Bult, Peter van Diest, Paul J. Derksen, Patrick W. B. |
author_sort | Vlug, Eva J. |
collection | PubMed |
description | BACKGROUND: Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. RESULTS: In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p < 0.001). Nuclear YAP expression did not associate with other variables such as lymph node involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types of invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p < 0.001) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer. CONCLUSIONS: Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13402-013-0143-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3777165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-37771652013-09-25 Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer Vlug, Eva J. van de Ven, Robert A. H. Vermeulen, Jeroen F. Bult, Peter van Diest, Paul J. Derksen, Patrick W. B. Cell Oncol (Dordr) Original Paper BACKGROUND: Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. RESULTS: In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p < 0.001). Nuclear YAP expression did not associate with other variables such as lymph node involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types of invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p < 0.001) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer. CONCLUSIONS: Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13402-013-0143-7) contains supplementary material, which is available to authorized users. Springer Netherlands 2013-08-15 2013 /pmc/articles/PMC3777165/ /pubmed/23949920 http://dx.doi.org/10.1007/s13402-013-0143-7 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Paper Vlug, Eva J. van de Ven, Robert A. H. Vermeulen, Jeroen F. Bult, Peter van Diest, Paul J. Derksen, Patrick W. B. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title | Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title_full | Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title_fullStr | Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title_full_unstemmed | Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title_short | Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer |
title_sort | nuclear localization of the transcriptional coactivator yap is associated with invasive lobular breast cancer |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777165/ https://www.ncbi.nlm.nih.gov/pubmed/23949920 http://dx.doi.org/10.1007/s13402-013-0143-7 |
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