Lysophosphatidic acid modulates the association of PTP1B with N-cadherin/catenin complex in SKOV3 ovarian cancer cells
Journal
Cell Biology International
Journal Volume
36
Journal Issue
9
Pages
833-841
Date Issued
2012
Author(s)
Abstract
LPA (lysophosphatidic acid) is a natural phospholipid that plays important roles in promoting cancer cell proliferation, invasion and metastases. We previously reported that LPA induces ovarian cancer cell dispersal and disruption of AJ (adherens junction) through the activation of SFK (Src family kinases). In this study, we have investigated the regulatory mechanisms during the early phase of LPA-induced cell dispersal. An in vitro model of the ovarian cancer cell line SKOV3 for cell dispersal was used. LPA induces rapid AJ disruption by increasing the internalization of N-cadherin-β-catenin. By using immunoprecipitations, LPA was shown to induce increased tyrosine phosphorylation of β-catenin and alter the balance of β-catenin-bound SFK and PTP1B (phosphotyrosine phosphatase 1B). The altered balance of tyrosine kinase/phosphatase correlated with a concomitant disintegration of the β-catenin-α-catenin, but not the β-catenin-N-cadherin complex. This disintegration of β-catenin from α-catenin and the cell dispersal caused by LPA can be rescued by blocking SFK activity with the chemical inhibitor, PP2. More importantly, PP2 also restores the level of PTP1B bound to β-catenin. We propose that LPA signalling alters AJ stability by changing the dynamics of tyrosine kinase/phosphatase bound to AJ proteins. This work provides further understanding of the early signalling events regulating ovarian cancer cell dispersal and AJ disruption induced by LPA. ? The Author(s) Journal Compilation ? 2012 International Federation for Cell Biology.
SDGs
Other Subjects
4 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; alpha catenin; beta catenin; lysophosphatidic acid; nerve cell adhesion molecule; protein kinase Fyn; protein tyrosine kinase; protein tyrosine phosphatase 1B; article; cancer cell culture; cell junction; cell spreading; cellular distribution; controlled study; enzyme inhibition; in vitro study; internalization; ovary cancer; protein analysis; protein binding; protein modification; protein phosphorylation; protein protein interaction; regulatory mechanism; signal transduction
Publisher
Wiley-Blackwell Publishing Ltd
Type
journal article