Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway

Matrix stiffness potently regulates cellular behavior in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional...

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Main Authors:	Wei, Spencer C., Fattet, Laurent, Tsai, Jeff H., Guo, Yurong, Pai, Vincent H., Majeski, Hannah E., Chen, Albert C., Sah, Robert L., Taylor, Susan S., Engler, Adam J., Yang, Jing
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452027/

id	pubmed-4452027
recordtype	oai_dc
spelling	pubmed-44520272015-11-01 Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway Wei, Spencer C. Fattet, Laurent Tsai, Jeff H. Guo, Yurong Pai, Vincent H. Majeski, Hannah E. Chen, Albert C. Sah, Robert L. Taylor, Susan S. Engler, Adam J. Yang, Jing Article Matrix stiffness potently regulates cellular behavior in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechano-mediator that promotes epithelial-mesenchymal transition (EMT) in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fiber alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion, and metastasis. 2015-04-20 2015-05 /pmc/articles/PMC4452027/ /pubmed/25893917 http://dx.doi.org/10.1038/ncb3157 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wei, Spencer C. Fattet, Laurent Tsai, Jeff H. Guo, Yurong Pai, Vincent H. Majeski, Hannah E. Chen, Albert C. Sah, Robert L. Taylor, Susan S. Engler, Adam J. Yang, Jing
spellingShingle	Wei, Spencer C. Fattet, Laurent Tsai, Jeff H. Guo, Yurong Pai, Vincent H. Majeski, Hannah E. Chen, Albert C. Sah, Robert L. Taylor, Susan S. Engler, Adam J. Yang, Jing Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
author_facet	Wei, Spencer C. Fattet, Laurent Tsai, Jeff H. Guo, Yurong Pai, Vincent H. Majeski, Hannah E. Chen, Albert C. Sah, Robert L. Taylor, Susan S. Engler, Adam J. Yang, Jing
author_sort	Wei, Spencer C.
title	Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
title_short	Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
title_full	Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
title_fullStr	Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
title_full_unstemmed	Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway
title_sort	matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a twist1-g3bp2 mechanotransduction pathway
description	Matrix stiffness potently regulates cellular behavior in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechano-mediator that promotes epithelial-mesenchymal transition (EMT) in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fiber alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion, and metastasis.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452027/
_version_	1613230543928819712

Matrix stiffness drives Epithelial-Mesenchymal Transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway

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