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Lysophosphatidic acid induces ovarian cancer cell dispersal by activating Fyn kinase associated with p120‐catenin
Author(s) -
Huang Ruby YunJu,
Wang SeuMei,
Hsieh ChangYao,
Wu JiahnChun
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23579
Subject(s) - lysophosphatidic acid , microbiology and biotechnology , adherens junction , proto oncogene tyrosine protein kinase src , biology , tyrosine protein kinase csk , src family kinase , cell migration , cancer research , kinase , cell , cadherin , sh3 domain , biochemistry , receptor
Lysophosphatidic acid (LPA), known as the “ovarian cancer activating factor,” is a natural phospholipid involved in important biological functions, such as cell proliferation, wound healing and neurite retraction. LPA causes colony dispersal in various carcinoma cell lines by inducing morphological changes, including membrane ruffling, lamellipodia formation, cell–cell dissociation and single cell migration. However, its effects on cell–cell dissociation and cell–cell adhesion of ovarian cancer cells have not been studied. In our study, we showed that LPA induced sequential events of intercellular junction dispersal and “half‐junction” formation in ovarian cancer SKOV3 cells and that Src‐family kinases were involved in both processes, since the effects were abolished by the selective tyrosine kinase inhibitor PP2. LPA induced rapid and transient activation of Src family kinases, which were recruited to cell–cell junctions by increasing the association with the adherens junction protein p120‐catenin. We identified the Src family kinase, Fyn, as the key component associated with p120‐catenin after LPA stimulation in SKOV3 cells. Our study provides evidence that LPA induces junction dispersal in ovarian cancer SKOV3 cells by activating the Src family kinase Fyn and increasing its association with p120‐catenin at the cell–cell junction. © 2008 Wiley‐Liss, Inc.