Huang Ruby Yun-Ju, Wang Seu-Mei, Hsieh Chang-Yao, Wu Jiahn-Chun
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Int J Cancer. 2008 Aug 15;123(4):801-9. doi: 10.1002/ijc.23579.
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.
溶血磷脂酸（LPA），被称为“卵巢癌激活因子”，是一种参与细胞增殖、伤口愈合和神经突回缩等重要生物学功能的天然磷脂。LPA通过诱导包括膜皱襞、片状伪足形成、细胞间解离和单细胞迁移在内的形态学变化，导致多种癌细胞系中的集落分散。然而，其对卵巢癌细胞间解离和细胞间黏附的影响尚未得到研究。在我们的研究中，我们发现LPA在卵巢癌SKOV3细胞中诱导细胞间连接分散和“半连接”形成的一系列事件，并且Src家族激酶参与了这两个过程，因为选择性酪氨酸激酶抑制剂PP2消除了这些作用。LPA诱导Src家族激酶的快速和短暂激活，这些激酶通过增加与黏附连接蛋白p120-连环蛋白的结合而被招募到细胞间连接处。我们确定Src家族激酶Fyn是SKOV3细胞中LPA刺激后与p120-连环蛋白相关的关键成分。我们的研究提供了证据，表明LPA通过激活Src家族激酶Fyn并增加其在细胞间连接处与p120-连环蛋白的结合，诱导卵巢癌SKOV3细胞中的连接分散。
