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The Activated Insulin-Like Growth Factor I Receptor Induces Depolarization in Breast Epithelial Cells Characterized by Actin Filament Disassembly and Tyrosine Dephosphorylation of FAK, Cas, and Paxillin

The Activated Insulin-Like Growth Factor I Receptor Induces Depolarization in Breast Epithelial Cells Characterized by Actin Filament Disassembly and Tyrosine Dephosphorylation of FAK, Cas, and Paxillin

M A Guvakova, E Surmacz

Exp Cell Res. 1999 Aug 25;251(1):244-55.

PMID: 10438590

Abstract:

Insulin-like growth factor I (IGF-I) promotes the motility of different cell types. We investigated the role of IGF-I receptor (IGF-IR) signaling in locomotion of MCF-7 breast cancer epithelial cells overexpressing the wild-type IGF-IR (MCF-7/IGF-IR). Stimulation of MCF-7/IGF-IR cells with 50 ng/ml IGF-I induced disruption of the polarized cell monolayer followed by morphological transition toward a mesenchymal phenotype. Immunofluorescence staining of the cells with rhodamine-phalloidin revealed rapid disassembly of actin fibers and development of a cortical actin meshwork. Activation of phosphatidylinositol (PI)3-kinase downstream of the IGF-IR was necessary for this process, as blocking PI 3-kinase activity with the specific inhibitor LY 294002 at 10 microM prevented disruption of the filamentous actin. In parallel, IGF-IR activation induced rapid and transient tyrosine dephosphorylation of focal adhesion proteins p125 focal adhesion kinase (FAK), p130 Crk-associated substrate (Cas), and paxillin. This process required phosphotyrosine phosphatase (PTP) activity, since pretreatment of the cells with 5 microM phenylarsine oxide (PAO), an inhibitor of PTPs, rescued FAK and its associated proteins Cas and paxillin from IGF-I-induced dephosphorylation. In addition, PAO-pretreated cells were refractory to IGF-I-induced morphological transition. Thus, our findings reveal a new function of the IGF-IR, the ability to depolarize epithelial cells. In MCF-7 cells, mechanisms of IGF-IR-mediated cell depolarization involve PI 3-kinase signaling and putative PTP activities.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP154447366-B	LY 294002 - CAS 154447-36-6		154447-36-6	Price
AP4506665-B	Focal Adhesion Kinase Inhibitor I - CAS 4506-66-5		4506-66-5	Price

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