Brought to you by Portland Press Ltd.
Published on behalf of the International Federation for Cell Biology
Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2012) 36, 833–841 (Printed in Great Britain)
Lysophosphatidic acid modulates the association of PTP1B with N-cadherin/catenin complex in SKOV3 ovarian cancer cells
Ruby Yun‑Ju Huang*†, Chen‑Chen Wen‡, Chih‑Kai Liao‡, Shu‑Huei Wang‡, Liang‑Yin Chou§ and Jiahn‑Chun Wu§1
*Department of Obstetrics and Gynaecology, National University Hospital of Singapore, Singapore, †Cancer Science Institute of Singapore, National University of Singapore, Singapore, ‡Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, and §Department of Anatomy and Cell Biology, College of Medicine, National YangMing University, Taipei, Taiwan


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.


Key words: adherens junction, LPA, ovarian cancer, PTP1B, tyrosine kinase, Src

Abbreviations: AJ, adherens junction, ALP, alkaline phosphatase, EGFR, epidermal growth factor receptor, EMT, epithelial–mesenchymal transition, GAPDH, glyceraldehydes-3-phosphate dehydrogenase, GPCR, G protein-coupled receptor, HRP, horseradish peroxidase, LPA, lysophosphatidic acid, PTP1B, phosphotyrosine phosphatase 1B, RTK, receptor tyrosine kinase, SFK, Src family kinase, siRNA, small interfering RNA, TBS, Tris-buffered saline

1To whom correspondence should be addressed (email jcwu2@ym.edu.tw).


Received 30 December 2011/5 April 2012; accepted 14 May 2012

Published as Cell Biology International Immediate Publication 14 May 2012, doi:10.1042/CBI20110687


© The Author(s) Journal compilation © 2012 International Federation for Cell Biology


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)