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 ...Continue Reading
References
Sep 1, 1990·The Journal of Clinical Investigation·G B MillsA Marks
Jul 1, 1995·The Journal of Cell Biology·K A KnudsenM J Wheelock
Dec 1, 1994·The Journal of Cell Biology·H HoschuetzkyR Kemler
Nov 14, 1997·The Biochemical Journal·F Liu, J Chernoff
Jan 31, 1998·The EMBO Journal·H DaubA Ullrich
Sep 5, 1998·JAMA : the Journal of the American Medical Association·Y XuG Casey
Oct 24, 1998·The Journal of Cell Biology·J BalsamoJ Lilien
Jun 8, 2001·The Journal of Biological Chemistry·J TaoH Y Wang
Aug 14, 2001·The Journal of Biological Chemistry·J TaoH Y Wang
Sep 5, 2001·The EMBO Journal·F PalaciosC D'Souza-Schorey
Jun 19, 2002·Biochimica Et Biophysica Acta·Xianjun FangGordon B Mills
Oct 16, 2002·The Journal of Biological Chemistry·Gang XuJanne Balsamo
Mar 18, 2003·Molecular and Cellular Biology·Jose PiedraMireia Duñach
Aug 2, 2003·Nature Reviews. Cancer·Gordon B Mills, Wouter H Moolenaar
Jan 7, 2004·Cancer Cell·Zhimin LuTony Hunter
Jul 13, 2004·Biochimica Et Biophysica Acta·V G BruntonM C Frame
Oct 9, 2004·Carcinogenesis·Chia-Hung ChouChang-Yao Hsieh
Dec 25, 2004·The Journal of Biological Chemistry·Wei LiDavid C Spray
Aug 16, 2005·Current Opinion in Cell Biology·Jack Lilien, Janne Balsamo
May 29, 2008·International Journal of Cancer. Journal International Du Cancer·Ruby Yun-Ju HuangJiahn-Chun Wu
Nov 13, 2008·Journal of the National Cancer Institute·Shuangxing YuGordon B Mills
Feb 25, 2009·PloS One·Yoonseok Kam, Vito Quaranta
Jul 31, 2009·Molecular Biology of the Cell·Lidiya OrlichenkoMark A McNiven
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Citations
Jan 1, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sergejs BerdnikovsJoan M Cook-Mills
Jul 9, 2014·The Journal of Cell Biology·Sei KuriyamaRoberto Mayor
Mar 25, 2014·Free Radical Biology & Medicine·Chananat KlomsiriLarry W Daniel
Jun 28, 2014·Journal of Molecular Neuroscience : MN·Qiong ShiRutong Yu
Apr 12, 2017·Current Rheumatology Reports·Cristiano Sacchetti, Nunzio Bottini
Oct 8, 2020·Cytopathology : Official Journal of the British Society for Clinical Cytology·Ben DavidsonDag Andre Nymoen