P120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via β-catenin and Kaiso respectively.

<h4>Background</h4>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.<h4>Methods and findings</h4>We found that both cyclin D1 and cyclin E could be effectively restored by rest...

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Autores principales:	Guiyang Jiang, Yan Wang, Shundong Dai, Yang Liu, Maggie Stoecker, Endi Wang, Enhua Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a14b67098bd421ead5762b6c02d9c3a
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spelling	oai:doaj.org-article:1a14b67098bd421ead5762b6c02d9c3a2021-11-18T07:29:44ZP120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via β-catenin and Kaiso respectively.1932-620310.1371/journal.pone.0030303https://doaj.org/article/1a14b67098bd421ead5762b6c02d9c3a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22276175/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.Guiyang JiangYan WangShundong DaiYang LiuMaggie StoeckerEndi WangEnhua WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30303 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guiyang Jiang Yan Wang Shundong Dai Yang Liu Maggie Stoecker Endi Wang Enhua Wang P120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via β-catenin and Kaiso respectively.
description	<h4>Background</h4>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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	article
author	Guiyang Jiang Yan Wang Shundong Dai Yang Liu Maggie Stoecker Endi Wang Enhua Wang
author_facet	Guiyang Jiang Yan Wang Shundong Dai Yang Liu Maggie Stoecker Endi Wang Enhua Wang
author_sort	Guiyang Jiang
title	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_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_sort	p120-catenin isoforms 1 and 3 regulate proliferation and cell cycle of lung cancer cells via β-catenin and kaiso respectively.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1a14b67098bd421ead5762b6c02d9c3a
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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.

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