Cargando…

Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells

Vimentin is a Type III intermediate filament (VIF) cytoskeletal protein that regulates the mechanical and migratory behavior of cells. Its expression is considered to be a marker for the epithelial to mesenchymal transition (EMT) that takes place in tumor metastasis. However, the molecular mechanism...

Descripción completa

Detalles Bibliográficos
Autores principales: Sivagurunathan, Suganya, Vahabikashi, Amir, Yang, Haiqian, Zhang, Jun, Vazquez, Kelly, Rajasundaram, Dhivyaa, Politanska, Yuliya, Abdala-Valencia, Hiam, Notbohm, Jacob, Guo, Ming, Adam, Stephen A., Goldman, Robert D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527304/
https://www.ncbi.nlm.nih.gov/pubmed/36200046
http://dx.doi.org/10.3389/fcell.2022.929495
_version_ 1784801054922113024
author Sivagurunathan, Suganya
Vahabikashi, Amir
Yang, Haiqian
Zhang, Jun
Vazquez, Kelly
Rajasundaram, Dhivyaa
Politanska, Yuliya
Abdala-Valencia, Hiam
Notbohm, Jacob
Guo, Ming
Adam, Stephen A.
Goldman, Robert D.
author_facet Sivagurunathan, Suganya
Vahabikashi, Amir
Yang, Haiqian
Zhang, Jun
Vazquez, Kelly
Rajasundaram, Dhivyaa
Politanska, Yuliya
Abdala-Valencia, Hiam
Notbohm, Jacob
Guo, Ming
Adam, Stephen A.
Goldman, Robert D.
author_sort Sivagurunathan, Suganya
collection PubMed
description Vimentin is a Type III intermediate filament (VIF) cytoskeletal protein that regulates the mechanical and migratory behavior of cells. Its expression is considered to be a marker for the epithelial to mesenchymal transition (EMT) that takes place in tumor metastasis. However, the molecular mechanisms regulated by the expression of vimentin in the EMT remain largely unexplored. We created MCF7 epithelial cell lines expressing vimentin from a cumate-inducible promoter to address this question. When vimentin expression was induced in these cells, extensive cytoplasmic VIF networks were assembled accompanied by changes in the organization of the endogenous keratin intermediate filament networks and disruption of desmosomes. Significant reductions in intercellular forces by the cells expressing VIFs were measured by quantitative monolayer traction force and stress microscopy. In contrast, laser trapping micro-rheology revealed that the cytoplasm of MCF7 cells expressing VIFs was stiffer than the uninduced cells. Vimentin expression activated transcription of genes involved in pathways responsible for cell migration and locomotion. Importantly, the EMT related transcription factor TWIST1 was upregulated only in wild type vimentin expressing cells and not in cells expressing a mutant non-polymerized form of vimentin, which only formed unit length filaments (ULF). Taken together, our results suggest that vimentin expression induces a hybrid EMT correlated with the upregulation of genes involved in cell migration.
format Online
Article
Text
id pubmed-9527304
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95273042022-10-04 Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells Sivagurunathan, Suganya Vahabikashi, Amir Yang, Haiqian Zhang, Jun Vazquez, Kelly Rajasundaram, Dhivyaa Politanska, Yuliya Abdala-Valencia, Hiam Notbohm, Jacob Guo, Ming Adam, Stephen A. Goldman, Robert D. Front Cell Dev Biol Cell and Developmental Biology Vimentin is a Type III intermediate filament (VIF) cytoskeletal protein that regulates the mechanical and migratory behavior of cells. Its expression is considered to be a marker for the epithelial to mesenchymal transition (EMT) that takes place in tumor metastasis. However, the molecular mechanisms regulated by the expression of vimentin in the EMT remain largely unexplored. We created MCF7 epithelial cell lines expressing vimentin from a cumate-inducible promoter to address this question. When vimentin expression was induced in these cells, extensive cytoplasmic VIF networks were assembled accompanied by changes in the organization of the endogenous keratin intermediate filament networks and disruption of desmosomes. Significant reductions in intercellular forces by the cells expressing VIFs were measured by quantitative monolayer traction force and stress microscopy. In contrast, laser trapping micro-rheology revealed that the cytoplasm of MCF7 cells expressing VIFs was stiffer than the uninduced cells. Vimentin expression activated transcription of genes involved in pathways responsible for cell migration and locomotion. Importantly, the EMT related transcription factor TWIST1 was upregulated only in wild type vimentin expressing cells and not in cells expressing a mutant non-polymerized form of vimentin, which only formed unit length filaments (ULF). Taken together, our results suggest that vimentin expression induces a hybrid EMT correlated with the upregulation of genes involved in cell migration. Frontiers Media S.A. 2022-09-19 /pmc/articles/PMC9527304/ /pubmed/36200046 http://dx.doi.org/10.3389/fcell.2022.929495 Text en Copyright © 2022 Sivagurunathan, Vahabikashi, Yang, Zhang, Vazquez, Rajasundaram, Politanska, Abdala-Valencia, Notbohm, Guo, Adam and Goldman. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sivagurunathan, Suganya
Vahabikashi, Amir
Yang, Haiqian
Zhang, Jun
Vazquez, Kelly
Rajasundaram, Dhivyaa
Politanska, Yuliya
Abdala-Valencia, Hiam
Notbohm, Jacob
Guo, Ming
Adam, Stephen A.
Goldman, Robert D.
Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title_full Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title_fullStr Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title_full_unstemmed Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title_short Expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid EMT in human mammary epithelial cells
title_sort expression of vimentin alters cell mechanics, cell-cell adhesion, and gene expression profiles suggesting the induction of a hybrid emt in human mammary epithelial cells
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527304/
https://www.ncbi.nlm.nih.gov/pubmed/36200046
http://dx.doi.org/10.3389/fcell.2022.929495
work_keys_str_mv AT sivagurunathansuganya expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT vahabikashiamir expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT yanghaiqian expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT zhangjun expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT vazquezkelly expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT rajasundaramdhivyaa expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT politanskayuliya expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT abdalavalenciahiam expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT notbohmjacob expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT guoming expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT adamstephena expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells
AT goldmanrobertd expressionofvimentinalterscellmechanicscellcelladhesionandgeneexpressionprofilessuggestingtheinductionofahybridemtinhumanmammaryepithelialcells