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Hic-5 promotes invadopodia formation and invasion during TGFß1-induced epithelial-mesenchymal transition

Hic-5 promotes invadopodia formation and invasion during TGFß1-induced epithelial-mesenchymal transition
Hic-5 promotes invadopodia formation and invasion during TGFß1-induced epithelial-mesenchymal transition
Transforming growth factor ß (TGF-ß)-stimulated epithelial-mesenchymal transition (EMT) is an important developmental process that has also been implicated in increased cell invasion and metastatic potential of cancer cells. Expression of the focal adhesion protein Hic-5 has been shown to be up-regulated in epithelial cells in response to TGF-ß. Herein, we demonstrate that TGF-ß-induced Hic-5 up-regulation or ectopic expression of Hic-5 in normal MCF10A cells promoted increased extracellular matrix degradation and invasion through the formation of invadopodia. Hic-5 was tyrosine phosphorylated in an Src-dependent manner after TGF-ß stimulation, and inhibition of Src activity or overexpression of a Y38/60F nonphosphorylatable mutant of Hic-5 inhibited matrix degradation and invasion. RhoC, but not RhoA, was also required for TGF-ß- and Hic-5-induced matrix degradation. Hic-5 also induced matrix degradation, cell migration, and invasion in the absence of TGF-ß via Rac1 regulation of p38 MAPK. These data identify Hic-5 as a critical mediator of TGF-ß-stimulated invadopodia formation, cell migration, and invasion
1540-8140
421-437
Pignatelli, Jeanine
b5db5e9d-b01e-4c86-b8fe-ce9f57bf03e3
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Schmidt, Ronald P.
13002e97-1f52-4bd1-93b8-2f9eebaed38b
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850
Pignatelli, Jeanine
b5db5e9d-b01e-4c86-b8fe-ce9f57bf03e3
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Schmidt, Ronald P.
13002e97-1f52-4bd1-93b8-2f9eebaed38b
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850

Pignatelli, Jeanine, Tumbarello, David A., Schmidt, Ronald P. and Turner, Christopher E. (2012) Hic-5 promotes invadopodia formation and invasion during TGFß1-induced epithelial-mesenchymal transition. The Journal of Cell Biology, 197 (3), 421-437. (doi:10.1083/jcb.201108143). (PMID:22529104)

Record type: Article

Abstract

Transforming growth factor ß (TGF-ß)-stimulated epithelial-mesenchymal transition (EMT) is an important developmental process that has also been implicated in increased cell invasion and metastatic potential of cancer cells. Expression of the focal adhesion protein Hic-5 has been shown to be up-regulated in epithelial cells in response to TGF-ß. Herein, we demonstrate that TGF-ß-induced Hic-5 up-regulation or ectopic expression of Hic-5 in normal MCF10A cells promoted increased extracellular matrix degradation and invasion through the formation of invadopodia. Hic-5 was tyrosine phosphorylated in an Src-dependent manner after TGF-ß stimulation, and inhibition of Src activity or overexpression of a Y38/60F nonphosphorylatable mutant of Hic-5 inhibited matrix degradation and invasion. RhoC, but not RhoA, was also required for TGF-ß- and Hic-5-induced matrix degradation. Hic-5 also induced matrix degradation, cell migration, and invasion in the absence of TGF-ß via Rac1 regulation of p38 MAPK. These data identify Hic-5 as a critical mediator of TGF-ß-stimulated invadopodia formation, cell migration, and invasion

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More information

e-pub ahead of print date: 23 April 2012
Published date: 30 April 2012
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 362403
URI: http://eprints.soton.ac.uk/id/eprint/362403
ISSN: 1540-8140
PURE UUID: 5fd28ffd-4aed-4671-8817-962b2dcd7ec7
ORCID for David A. Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561

Catalogue record

Date deposited: 22 Aug 2014 09:06
Last modified: 09 Nov 2021 03:32

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Contributors

Author: Jeanine Pignatelli
Author: Ronald P. Schmidt
Author: Christopher E. Turner

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