Graduate Center and Department of Biological Sciences, Hunter College, The City University of New York, New York, NY 10065, United States.
Cell Signal. 2012 Aug;24(8):1531-40. doi: 10.1016/j.cellsig.2012.03.015. Epub 2012 Mar 28.
MDA-MB-231 cells are highly aggressive human breast adenocarcinoma cells that depend on PLD activity for survival. In response to the stress of serum withdrawal, there is increased motility and invasiveness of these cells that is associated with a rapid increase in PLD activity. In addition, PLD activity is elevated in response to most mitogenic signals. Similar to PLD, paxillin, a focal adhesion adaptor protein, and Erk, mitogen-activated protein kinase, play vital roles in cell motility through regulation of focal adhesion dynamics. Here, we addressed whether there is a functional correlation between paxillin and PLD that may influence cancer cell motility. We investigated the role of PLD activity on paxillin regulation, Erk activation and formation of a paxillin-Erk and paxillin-FAK association. Inhibition of PLD activity led to an increase in paxillin tyrosine phosphorylation, a decrease in Erk activation, as measured by phosphorylation, and enhanced association of paxillin with Erk. In addition, we found that paxillin tyrosine phosphorylation depends upon Erk activity and may be a consequence of an increased association with FAK. Taken together, these results suggest that Erk activity is governed by PLD activity and regulates the tyrosine phosphorylation of paxillin, potentially explaining its role in cell motility. This study indicated that PLD, Erk, paxillin and FAK participate in the same signaling pathway in this breast cancer cell line.
MDA-MB-231 细胞是高度侵袭性的人乳腺癌腺癌细胞，其生存依赖于 PLD 活性。在血清剥夺的应激反应中，这些细胞的迁移和侵袭能力增强，与 PLD 活性的快速增加有关。此外，PLD 活性还会对大多数有丝分裂信号作出响应而升高。与 PLD 类似，粘着斑衔接蛋白 paxillin 和丝裂原活化蛋白激酶 Erk 通过调节粘着斑动力学在细胞迁移中发挥重要作用。在这里，我们探讨了 paxillin 和 PLD 之间是否存在功能相关性，这可能会影响癌细胞的迁移能力。我们研究了 PLD 活性对 paxillin 调节、Erk 激活以及 paxillin-Erk 和 paxillin-FAK 关联形成的作用。PLD 活性的抑制导致 paxillin 酪氨酸磷酸化增加，Erk 激活减少（通过磷酸化测量），并增强了 paxillin 与 Erk 的关联。此外，我们发现 paxillin 酪氨酸磷酸化依赖于 Erk 活性，可能是与 FAK 关联增加的结果。总之，这些结果表明，Erk 活性受 PLD 活性的控制，并调节 paxillin 的酪氨酸磷酸化，这可能解释了其在细胞迁移中的作用。这项研究表明，在这种乳腺癌细胞系中，PLD、Erk、paxillin 和 FAK 参与了相同的信号通路。
