Department of Biosciences, Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland.
Biomolecules. 2013 May 14;3(2):303-15. doi: 10.3390/biom3020303.
Sphingomyelin is found in the cell membrane of all eukaryotic cells, and was for a long time considered merely as a structural component. However, during the last two decades, metabolites of sphingomyelin, especially sphingosine 1-phosphate (S1P), have proven to be physiologically significant regulators of cell function. Through its five different G protein-coupled receptors, S1P regulates a wide array of cellular processes, ranging from stimulating cellular proliferation and migration, to the inhibition of apoptosis and induction of angiogenesis and modulation of cellular calcium homeostasis. Many of the processes regulated by S1P are important for normal cell physiology, but may also induce severe pathological conditions, especially in malignancies like cancer. Thus, understanding S1P signaling mechanisms has been the aim of a multitude of investigations. Great interest has also been shown in understanding the action of sphingosine kinase (SphK), i.e., the kinase phosphorylating sphingosine to S1P, and the interactions between S1P and growth factor signaling. In the present review, we will discuss recent findings regarding the possible importance of S1P and SphK in the etiology of thyroid cancer. Although clinical data is still scarce, our in vitro findings suggest that S1P may function as a "double-edged sword", as the receptor profile of thyroid cancer cells largely determines whether S1P stimulates or blocks cellular migration. We will also discuss the interactions between S1P- and VEGF-evoked signaling, and the importance of a S1P1-VEGF receptor 2 complex in thyroid cancer cells.
鞘磷脂存在于所有真核细胞的细胞膜中，长期以来一直被认为仅仅是一种结构成分。然而，在过去的二十年中，鞘磷脂的代谢产物，特别是 1-磷酸鞘氨醇（S1P），已被证明是细胞功能的生理上重要的调节剂。通过其五个不同的 G 蛋白偶联受体，S1P 调节广泛的细胞过程，从刺激细胞增殖和迁移，到抑制细胞凋亡和诱导血管生成以及调节细胞钙稳态。S1P 调节的许多过程对正常细胞生理学很重要，但也可能诱导严重的病理状况，特别是在癌症等恶性肿瘤中。因此，理解 S1P 信号转导机制一直是众多研究的目标。人们对理解鞘氨醇激酶（SphK）的作用，即磷酸化鞘氨醇生成 S1P 的激酶，以及 S1P 与生长因子信号之间的相互作用也表现出极大的兴趣。在本综述中，我们将讨论最近关于 S1P 和 SphK 在甲状腺癌发病机制中的可能重要性的发现。尽管临床数据仍然匮乏，但我们的体外研究结果表明，S1P 可能作为一把“双刃剑”发挥作用，因为甲状腺癌细胞的受体谱在很大程度上决定了 S1P 是刺激还是阻断细胞迁移。我们还将讨论 S1P-和 VEGF 引发的信号之间的相互作用，以及 S1P1-VEGF 受体 2 复合物在甲状腺癌细胞中的重要性。
