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P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively
BACKGROUND: The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date. METHODS AND FINDINGS: We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262806/ https://www.ncbi.nlm.nih.gov/pubmed/22276175 http://dx.doi.org/10.1371/journal.pone.0030303 |
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author | Jiang, Guiyang Wang, Yan Dai, Shundong Liu, Yang Stoecker, Maggie Wang, Endi Wang, Enhua |
author_facet | Jiang, Guiyang Wang, Yan Dai, Shundong Liu, Yang Stoecker, Maggie Wang, Endi Wang, Enhua |
author_sort | Jiang, Guiyang |
collection | PubMed |
description | BACKGROUND: The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date. METHODS AND FINDINGS: We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A in p120ctn depleted lung cancer cells. When the expression of cyclin D1 was blocked by co-transfection with siRNA-cyclin D1 in p120ctn depleted cells restoring p120ctn-1A or 3A, the expression of cyclin E was slightly decreased, not increased, implying that p120ctn isoforms 1 and 3 cannot up-regulate cyclin E directly but may do so through up-regulation of cyclin D1. Interestingly, overexpression of p120ctn-1A increased β-catenin and cyclin D1 expression, while co-transfection with siRNA targeting β-catenin abolishes the effect of p120ctn-1A on up-regulation of cyclin D1, suggesting a role of β-catenin in mediating p120ctn-1A's regulatory function on cyclin D1 expression. On the other hand, overexpression of p120ctn isoform 3A reduced nuclear Kaiso localization, thus decreasing the binding of Kaiso to KBS on the cyclin D1 promoter and thereby enhancing the expression of cyclin D1 gene by relieving the repressor effect of Kaiso. Because overexpressing NLS-p120ctn-3A (p120ctn-3A nuclear target localization plasmids) or inhibiting nuclear export of p120ctn-3 by Leptomycin B (LMB) caused translocation of Kaiso to the nucleus, it is plausible that the nuclear export of Kaiso is p120ctn-3-dependent. CONCLUSIONS: Our results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells probably via different protein mediators, namely, β-catenin for isoform 1 and Kaiso, a negative transcriptional factor of cyclin D1, for isoform 3. |
format | Online Article Text |
id | pubmed-3262806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32628062012-01-24 P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively Jiang, Guiyang Wang, Yan Dai, Shundong Liu, Yang Stoecker, Maggie Wang, Endi Wang, Enhua PLoS One Research Article BACKGROUND: The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date. METHODS AND FINDINGS: We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A in p120ctn depleted lung cancer cells. When the expression of cyclin D1 was blocked by co-transfection with siRNA-cyclin D1 in p120ctn depleted cells restoring p120ctn-1A or 3A, the expression of cyclin E was slightly decreased, not increased, implying that p120ctn isoforms 1 and 3 cannot up-regulate cyclin E directly but may do so through up-regulation of cyclin D1. Interestingly, overexpression of p120ctn-1A increased β-catenin and cyclin D1 expression, while co-transfection with siRNA targeting β-catenin abolishes the effect of p120ctn-1A on up-regulation of cyclin D1, suggesting a role of β-catenin in mediating p120ctn-1A's regulatory function on cyclin D1 expression. On the other hand, overexpression of p120ctn isoform 3A reduced nuclear Kaiso localization, thus decreasing the binding of Kaiso to KBS on the cyclin D1 promoter and thereby enhancing the expression of cyclin D1 gene by relieving the repressor effect of Kaiso. Because overexpressing NLS-p120ctn-3A (p120ctn-3A nuclear target localization plasmids) or inhibiting nuclear export of p120ctn-3 by Leptomycin B (LMB) caused translocation of Kaiso to the nucleus, it is plausible that the nuclear export of Kaiso is p120ctn-3-dependent. CONCLUSIONS: Our results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells probably via different protein mediators, namely, β-catenin for isoform 1 and Kaiso, a negative transcriptional factor of cyclin D1, for isoform 3. Public Library of Science 2012-01-20 /pmc/articles/PMC3262806/ /pubmed/22276175 http://dx.doi.org/10.1371/journal.pone.0030303 Text en Jiang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Jiang, Guiyang Wang, Yan Dai, Shundong Liu, Yang Stoecker, Maggie Wang, Endi Wang, Enhua P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title | P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title_full | P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title_fullStr | P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title_full_unstemmed | P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title_short | P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via β-Catenin and Kaiso Respectively |
title_sort | p120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via β-catenin and kaiso respectively |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262806/ https://www.ncbi.nlm.nih.gov/pubmed/22276175 http://dx.doi.org/10.1371/journal.pone.0030303 |
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