Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0614, USA.
FEBS Lett. 2010 Sep 24;584(18):4077-82. doi: 10.1016/j.febslet.2010.08.035. Epub 2010 Sep 7.
In MKN1 gastric cancer cells, lysophosphatidic acid (LPA) upregulates expression of sphingosine kinase 1 (SphK1) and its downregulation or inhibition suppresses LPA mediated proliferation. Although LPA activates numerous signaling pathways downstream of its receptors, including extracellular-signal-regulated kinase 1/2, p38, JNK, and Akt, and the transactivation of the epidermal growth factor receptor, pharmacological and molecular approaches demonstrated that only activation of ERK1, in addition to the CCAAT/enhancer-binding protein β transcription factor, is involved in transcriptional upregulation of SphK1 by LPA. Our data implicate ERK1 as an important mediator of LPA signaling leading to upregulation of SphK1 and point to SphK1 and sphingosine-1-phosphate production as potential therapeutic targets in gastric cancer.
在 MKN1 胃癌细胞中，溶血磷脂酸（LPA）上调鞘氨醇激酶 1（SphK1）的表达，其下调或抑制可抑制 LPA 介导的增殖。尽管 LPA 通过其受体下游激活许多信号通路，包括细胞外信号调节激酶 1/2、p38、JNK 和 Akt，以及表皮生长因子受体的转激活，但药理学和分子方法表明，只有 ERK1 的激活，除了 CCAAT/增强子结合蛋白 β 转录因子，参与 LPA 对 SphK1 的转录上调。我们的数据表明 ERK1 是 LPA 信号传导的重要介质，导致 SphK1 的上调，并指出 SphK1 和 1-磷酸鞘氨醇的产生可能是胃癌的潜在治疗靶点。
