Overexpression of the integrin-linked kinase mesenchymally transforms mammary epithelial cells

Citation
A. Somasiri et al., Overexpression of the integrin-linked kinase mesenchymally transforms mammary epithelial cells, J CELL SCI, 114(6), 2001, pp. 1125-1136
Citations number
72
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL SCIENCE
ISSN journal
0021-9533 → ACNP
Volume
114
Issue
6
Year of publication
2001
Pages
1125 - 1136
Database
ISI
SICI code
0021-9533(200103)114:6<1125:OOTIKM>2.0.ZU;2-H
Abstract
Signals generated by the interaction of pi integrins with laminin in the ba sement membrane contribute to mammary epithelial cell morphogenesis and dif ferentiation. The integrin-linked kinase (ILK) is one of the signaling moie ties that associates with the cytoplasmic domain of pr integrin subunits wi th some specificity. Forced expression of a dominant negative, kinase-dead form of ILK subtly altered mouse mammary epithelial cell morphogenesis but it did not prevent differentiative milk protein expression. In contrast, fo rced overexpression of wild-type ILK strongly inhibited both morphogenesis and differentiation. Overexpression of wild-type ILK also caused the cells to lose the cell-cell adhesion molecule E-cadherin, become invasive, reorga nize cortical actin into cytoplasmic stress fibers, and switch from an epit helial cytokeratin to a mesenchymal vimentin intermediate filament phenotyp e, Forced expression of E-cadherin in the latter mesenchymal cells rescued epithelial cytokeratin expression and it partially restored the ability of the cells to differentiate and undergo morphogenesis, These data demonstrat e that ILK, which responds to interactions between cells and the extracellu lar matrix, induces a mesenchymal transformation in mammary epithelial cell s, at least in part, by disrupting cell-cell junctions.