PO.CL01.17 · 临床研究
鞘氨醇激酶2（SPHK2）的阴阳两面：核定位与胞质定位在肺癌进展中的相反调控
The Yin and Yang of sphingosine kinase 2 (SPHK2): Opposing regulation by nuclear and cytoplasmic localization in lung cancer progression
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
1-磷酸鞘氨醇（S1P）是一种多效性脂质介质，主要由SPHK1和SPHK2生成，调控细胞存活、迁移和血管生成。尽管SPHK1和SPHK2已被报道为癌基因，我们对TCGA-LUAD（肺腺癌）的预后分析揭示了这两种酶的相反作用，提示SPHK2具有双重功能。我们研究了SPHK2假设的抑癌功能。与SPHK1不同，SPHK2能够进行核定位。我们的数据显示，组织中高水平的核定位SPHK2与肺癌患者较好的预后相关。在细胞核内过表达SPHK2显著降低了细胞增殖和迁移能力。此外，SPHK2的整体过表达增强了对药物FTY720的敏感性，但当SPHK2特异性地在细胞核内过表达时，这种敏感性降低。这表明SPHK2在胞质与核内的定位导致了相反的功能。TCGA-LUAD表达谱可能反映了SPHK2占主导的抑癌作用，因为其表达中更高比例位于核内。
查看英文原文 English abstract
Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator, generated primarily by SPHK1 and SPHK2, regulating cell survival, migration, and angiogenesis. While SPHK1 and SPHK2 have been reported as oncogenes, our prognostic analysis of TCGA-LUAD (Lung Adenocarcinoma) revealed opposite roles for the two enzymes, suggesting a dual function for SPHK2. We investigated the hypothesized tumor suppressor function of SPHK2. Unlike SPHK1, SPHK2 is capable of nuclear localization. Our data showed that high levels of nuclear-localized SPHK2 in tissue correlate with a better prognosis for lung cancer patients. Overexpression of SPHK2 within the nucleus significantly reduced cell proliferation and migration capacity. Furthermore, general SPHK2 overexpression enhanced sensitivity to the drug FTY720, but this sensitivity was reduced when SPHK2 was overexpressed specifically in the nucleus. This suggests that the localization of SPHK2 in the cytoplasm versus the nucleus results in opposing functions. The TCGA-LUAD expression profile likely reflects SPHK2's dominant tumor-suppressor role due to a higher proportion of its expression being nuclear.
利益披露 Disclosure
T. Lai, None..
W. Lee, None..
J. Chang, None.