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

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. Journal of Cell Biology, 197 (3), 421-437. (doi:10.1083/jcb.201108143). (PMID:22529104)

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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Contributors

Author: David A. Tumbarello

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