Aoyagi Tomoyoshi, Nagahashi Masayuki, Yamada Akimitsu, Takabe Kazuaki
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, Virginia 23298-0011, USA.
Lymphat Res Biol. 2012 Sep;10(3):97-106. doi: 10.1089/lrb.2012.0010.
Sphingosine-1-phosphate (S1P) is a potent sphingolipid metabolite that regulates a number of biological processes critical for cancer. S1P produced inside cancer cells is exported and exerts its extracellular functions by binding to its specific receptors in an autocrine, paracrine, and/or endocrine manner, which is known as inside-out signaling. S1P is also known to exert its intracellular functions especially in the inflammatory process, but its relevance to cancer biology remains to be elucidated. Recently, there have been growing interests in the role of S1P in breast cancer progression, including angiogenesis and lymphangiogenesis. Our group demonstrated that activation of sphingosine kinase 1, the enzyme that catalyzes the phosphorylation of sphingosine to S1P, is a key step of this process. In this review, we will cover our current knowledge on the role of S1P signaling pathway in breast cancer progression with an emphasis on its role in tumor-induced lymphangiogenesis.
1-磷酸鞘氨醇（S1P）是一种强效的鞘脂代谢产物，它调节许多对癌症至关重要的生物学过程。癌细胞内产生的S1P被输出，并通过以自分泌、旁分泌和/或内分泌方式与其特定受体结合来发挥其细胞外功能，这被称为由内而外信号传导。已知S1P也发挥其细胞内功能，尤其是在炎症过程中，但其与癌症生物学的相关性仍有待阐明。最近，人们对S1P在乳腺癌进展中的作用，包括血管生成和淋巴管生成，越来越感兴趣。我们的研究小组证明，鞘氨醇激酶1（催化鞘氨醇磷酸化为S1P的酶）的激活是这一过程的关键步骤。在这篇综述中，我们将阐述我们目前对S1P信号通路在乳腺癌进展中的作用的认识，重点是其在肿瘤诱导的淋巴管生成中的作用。
