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
- PMID: 10438590
- DOI: 10.1006/excr.1999.4566
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
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.
Copyright 1999 Academic Press.
Similar articles
-
Activation of m3 muscarinic receptors induces rapid tyrosine phosphorylation of p125(FAK), p130(cas), and paxillin in rat pancreatic acini.Arch Biochem Biophys. 2000 May 1;377(1):85-94. doi: 10.1006/abbi.2000.1761. Arch Biochem Biophys. 2000. PMID: 10775445
-
Insulin-like growth factor I stimulates tyrosine phosphorylation of p130(Cas), focal adhesion kinase, and paxillin. Role of phosphatidylinositol 3'-kinase and formation of a p130(Cas).Crk complex.J Biol Chem. 1998 Oct 2;273(40):26149-56. doi: 10.1074/jbc.273.40.26149. J Biol Chem. 1998. PMID: 9748296
-
EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas).Nat Cell Biol. 2002 Aug;4(8):565-73. doi: 10.1038/ncb823. Nat Cell Biol. 2002. PMID: 12134157
-
Tyrosine phosphorylation in the action of neuropeptides and growth factors.Essays Biochem. 1997;32:73-86. Essays Biochem. 1997. PMID: 9493012 Review.
-
Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists.J Cell Physiol. 1998 Dec;177(4):507-17. doi: 10.1002/(SICI)1097-4652(199812)177:4<507::AID-JCP2>3.0.CO;2-K. J Cell Physiol. 1998. PMID: 10092204 Review.
Cited by
-
Epithelial-to-mesenchymal transition in breast cancer: a role for insulin-like growth factor I and insulin-like growth factor-binding protein 3?Breast Cancer (Dove Med Press). 2015 Jan 19;7:9-19. doi: 10.2147/BCTT.S43932. eCollection 2015. Breast Cancer (Dove Med Press). 2015. PMID: 25632238 Free PMC article. Review.
-
Interaction of protein tyrosine phosphatase (PTP) 1B with its substrates is influenced by two distinct binding domains.Biochem J. 2002 Jun 1;364(Pt 2):377-83. doi: 10.1042/BJ20011372. Biochem J. 2002. PMID: 12023880 Free PMC article.
-
mTOR signaling in cancer cell motility and tumor metastasis.Crit Rev Eukaryot Gene Expr. 2010;20(1):1-16. doi: 10.1615/critreveukargeneexpr.v20.i1.10. Crit Rev Eukaryot Gene Expr. 2010. PMID: 20528734 Free PMC article. Review.
-
Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase.Mol Cell Biol. 2001 Jun;21(12):4016-31. doi: 10.1128/MCB.21.12.4016-4031.2001. Mol Cell Biol. 2001. PMID: 11359909 Free PMC article.
-
Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail.Mol Cell Biol. 2007 Apr;27(8):3165-75. doi: 10.1128/MCB.01315-06. Epub 2007 Feb 12. Mol Cell Biol. 2007. PMID: 17296734 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous
