CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
Anticancer Agents Med Chem. 2011 Nov;11(9):854-62. doi: 10.2174/187152011797655050.
Hypoxia, defined as reduced tissue oxygen concentration, is a characteristic of solid tumors and is an indicator of unfavorable diagnosis in patients. At the cellular level, the adaptation to hypoxia is under the control of two related transcription factors, HIF-1α and HIF-2α (Hypoxia-Inducible Factor), which activate expression of genes promoting angiogenesis, metastasis, increased tumor growth and resistance to treatments. A role for HIF-1α and HIF-2α is also emerging in hematologic malignancies such as lymphoma and l eukemia. Recent studies have identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway - which elicits various cellular processes including cell proliferation, cell survival or angiogenesis - as a new regulator of HIF-1α or HIF-2α activity. This review will consider how targeting the SphK1/S1P signaling could represent an attractive strategy for therapeutic intervention in cancer.
缺氧是指组织氧浓度降低，是实体瘤的特征之一，也是患者预后不良的指标。在细胞水平上，缺氧适应受两个相关的转录因子 HIF-1α 和 HIF-2α（缺氧诱导因子）的控制，它们激活促进血管生成、转移、肿瘤生长和治疗抵抗的基因表达。HIF-1α 和 HIF-2α 在淋巴瘤和白血病等血液恶性肿瘤中也发挥作用。最近的研究表明，鞘氨醇激酶 1/鞘氨醇 1-磷酸（SphK1/S1P）信号通路——引发包括细胞增殖、细胞存活或血管生成在内的各种细胞过程——是 HIF-1α 或 HIF-2α 活性的新调节剂。这篇综述将探讨靶向 SphK1/S1P 信号通路是否可能成为癌症治疗干预的一种有吸引力的策略。
