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

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.

Authors+Show Affiliations

Kimmel Cancer Institute, Thomas Jefferson University, 233 South 10th Street, B.L.S.B. 606, Philadelphia, Pennsylvania 19107, USA. Marina.Guvakova@mail.tju.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10438590

Citation

Guvakova, M A., and E Surmacz. "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." Experimental Cell Research, vol. 251, no. 1, 1999, pp. 244-55.
Guvakova MA, Surmacz E. 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. Exp Cell Res. 1999;251(1):244-55.
Guvakova, M. A., & Surmacz, E. (1999). 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. Experimental Cell Research, 251(1), 244-55.
Guvakova MA, Surmacz E. 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. Exp Cell Res. 1999 Aug 25;251(1):244-55. PubMed PMID: 10438590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Guvakova,M A, AU - Surmacz,E, PY - 1999/8/10/pubmed PY - 1999/8/10/medline PY - 1999/8/10/entrez SP - 244 EP - 55 JF - Experimental cell research JO - Exp Cell Res VL - 251 IS - 1 N2 - 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. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/10438590/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(99)94566-4 DB - PRIME DP - Unbound Medicine ER -