Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices.
Mol Biol Cell
; 29(13): 1704-1717, 2018 07 15.
Article
em En
| MEDLINE
| ID: mdl-29771639
ABSTRACT
The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell types have not been evaluated. Herein, utilizing 3D cell-derived matrices and fibronectin-coated one-dimensional substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity, and in vitro invasiveness. Domain mapping studies reveal sites critical to the functions of both Hic-5 and paxillin in regulating phenotype, while ectopic expression of Hic-5 in cell lines with low endogenous levels of the protein is sufficient to induce a Rac1-dependent mesenchymal phenotype and, in turn, increase amoeboid-mesenchymal plasticity and invasion. We show that the activity of vinculin, when coupled to the expression of Hic-5 is required for the mesenchymal morphology in the 3D ECM. Taken together, our results identify Hic-5 as a critical modulator of tumor cell phenotype that could be utilized in predicting tumor cell migratory and invasive behavior in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Peptídeos e Proteínas de Sinalização Intracelular
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Forma Celular
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Matriz Extracelular
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Proteínas com Domínio LIM
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Plasticidade Celular
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article