Lysophosphatidic acid induces ovarian cancer cell dispersal by activating Fyn kinase associated with p120-catenin
Journal
International Journal of Cancer
Journal Volume
123
Journal Issue
4
Pages
801-809
Date Issued
2008
Author(s)
Abstract
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.
SDGs
Other Subjects
beta catenin; catenin; lysophosphatidic acid; p120 catenin; protein kinase Fyn; 4 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; alpha catenin; cadherin associated Src substrate p120; cadherin-associated Src substrate p120; cell adhesion molecule; FYN protein, human; lysophosphatidic acid; lysophospholipid; phosphoprotein; protein kinase Fyn; protein kinase inhibitor; protein tyrosine kinase; pyrimidine derivative; article; biological activity; cancer cell; cell adhesion; cell function; cell junction; cell proliferation; cell structure; human; human cell; ovary cancer; priority journal; wound healing; cell junction; dose response; drug antagonism; drug effect; enzyme activation; enzymology; female; metabolism; ovary tumor; pathology; tumor cell line; Adherens Junctions; alpha Catenin; Cell Adhesion Molecules; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme Activation; Female; Humans; Lysophospholipids; Ovarian Neoplasms; Phosphoproteins; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-fyn; Pyrimidines; src-Family Kinases
Type
journal article