| First Author | Pignatelli J | Year | 2012 |
| Journal | J Cell Biol | Volume | 197 |
| Issue | 3 | Pages | 421-37 |
| PubMed ID | 22529104 | Mgi Jnum | J:185035 |
| Mgi Id | MGI:5427270 | Doi | 10.1083/jcb.201108143 |
| Citation | Pignatelli J, et al. (2012) Hic-5 promotes invadopodia formation and invasion during TGF-beta-induced epithelial-mesenchymal transition. J Cell Biol 197(3):421-37 |
| abstractText | Transforming growth factor beta (TGF-beta)-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-beta. Herein, we demonstrate that TGF-beta-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-beta 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-beta- and Hic-5-induced matrix degradation. Hic-5 also induced matrix degradation, cell migration, and invasion in the absence of TGF-beta via Rac1 regulation of p38 MAPK. These data identify Hic-5 as a critical mediator of TGF-beta-stimulated invadopodia formation, cell migration, and invasion. |
