Cargando…

By moonlighting in the nucleus, villin regulates epithelial plasticity

Villin is a tissue-specific, actin-binding protein involved in the assembly and maintenance of microvilli in polarized epithelial cells. Conversely, villin is also linked with the loss of epithelial polarity and gain of the mesenchymal phenotype in migrating, invasive cells. In this study, we descri...

Descripción completa

Detalles Bibliográficos
Autores principales: Patnaik, Srinivas, George, Sudeep P., Pham, Eric, Roy, Swati, Singh, Kanchan, Mariadason, John M., Khurana, Seema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751603/
https://www.ncbi.nlm.nih.gov/pubmed/26658611
http://dx.doi.org/10.1091/mbc.E15-06-0453
_version_ 1782415613178675200
author Patnaik, Srinivas
George, Sudeep P.
Pham, Eric
Roy, Swati
Singh, Kanchan
Mariadason, John M.
Khurana, Seema
author_facet Patnaik, Srinivas
George, Sudeep P.
Pham, Eric
Roy, Swati
Singh, Kanchan
Mariadason, John M.
Khurana, Seema
author_sort Patnaik, Srinivas
collection PubMed
description Villin is a tissue-specific, actin-binding protein involved in the assembly and maintenance of microvilli in polarized epithelial cells. Conversely, villin is also linked with the loss of epithelial polarity and gain of the mesenchymal phenotype in migrating, invasive cells. In this study, we describe for the first time how villin can switch between these disparate functions to change tissue architecture by moonlighting in the nucleus. Our study reveals that the moonlighting function of villin in the nucleus may play an important role in tissue homeostasis and disease. Villin accumulates in the nucleus during wound repair, and altering the cellular microenvironment by inducing hypoxia increases the nuclear accumulation of villin. Nuclear villin is also associated with mouse models of tumorigenesis, and a systematic analysis of a large cohort of colorectal cancer specimens confirmed the nuclear distribution of villin in a subset of tumors. Our study demonstrates that nuclear villin regulates epithelial–mesenchymal transition (EMT). Altering the nuclear localization of villin affects the expression and activity of Slug, a key transcriptional regulator of EMT. In addition, we find that villin directly interacts with a transcriptional corepressor and ligand of the Slug promoter, ZBRK1. The outcome of this study underscores the role of nuclear villin and its binding partner ZBRK1 in the regulation of EMT and as potential new therapeutic targets to inhibit tumorigenesis.
format Online
Article
Text
id pubmed-4751603
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-47516032016-04-16 By moonlighting in the nucleus, villin regulates epithelial plasticity Patnaik, Srinivas George, Sudeep P. Pham, Eric Roy, Swati Singh, Kanchan Mariadason, John M. Khurana, Seema Mol Biol Cell Articles Villin is a tissue-specific, actin-binding protein involved in the assembly and maintenance of microvilli in polarized epithelial cells. Conversely, villin is also linked with the loss of epithelial polarity and gain of the mesenchymal phenotype in migrating, invasive cells. In this study, we describe for the first time how villin can switch between these disparate functions to change tissue architecture by moonlighting in the nucleus. Our study reveals that the moonlighting function of villin in the nucleus may play an important role in tissue homeostasis and disease. Villin accumulates in the nucleus during wound repair, and altering the cellular microenvironment by inducing hypoxia increases the nuclear accumulation of villin. Nuclear villin is also associated with mouse models of tumorigenesis, and a systematic analysis of a large cohort of colorectal cancer specimens confirmed the nuclear distribution of villin in a subset of tumors. Our study demonstrates that nuclear villin regulates epithelial–mesenchymal transition (EMT). Altering the nuclear localization of villin affects the expression and activity of Slug, a key transcriptional regulator of EMT. In addition, we find that villin directly interacts with a transcriptional corepressor and ligand of the Slug promoter, ZBRK1. The outcome of this study underscores the role of nuclear villin and its binding partner ZBRK1 in the regulation of EMT and as potential new therapeutic targets to inhibit tumorigenesis. The American Society for Cell Biology 2016-02-01 /pmc/articles/PMC4751603/ /pubmed/26658611 http://dx.doi.org/10.1091/mbc.E15-06-0453 Text en © 2016 Patnaik, George, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Patnaik, Srinivas
George, Sudeep P.
Pham, Eric
Roy, Swati
Singh, Kanchan
Mariadason, John M.
Khurana, Seema
By moonlighting in the nucleus, villin regulates epithelial plasticity
title By moonlighting in the nucleus, villin regulates epithelial plasticity
title_full By moonlighting in the nucleus, villin regulates epithelial plasticity
title_fullStr By moonlighting in the nucleus, villin regulates epithelial plasticity
title_full_unstemmed By moonlighting in the nucleus, villin regulates epithelial plasticity
title_short By moonlighting in the nucleus, villin regulates epithelial plasticity
title_sort by moonlighting in the nucleus, villin regulates epithelial plasticity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751603/
https://www.ncbi.nlm.nih.gov/pubmed/26658611
http://dx.doi.org/10.1091/mbc.E15-06-0453
work_keys_str_mv AT patnaiksrinivas bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT georgesudeepp bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT phameric bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT royswati bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT singhkanchan bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT mariadasonjohnm bymoonlightinginthenucleusvillinregulatesepithelialplasticity
AT khuranaseema bymoonlightinginthenucleusvillinregulatesepithelialplasticity