Kalhori Veronica, Törnquist Kid
Department of Biosciences, Åbo Akademi University, Biocity, Artillerigatan 6, Turku 20520, Finland; The Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, Helsinki 00290, Finland.
Department of Biosciences, Åbo Akademi University, Biocity, Artillerigatan 6, Turku 20520, Finland; The Minerva Foundation Institute for Medical Research, Biomedicum Helsinki, Helsinki 00290, Finland.
Mol Cell Endocrinol. 2015 Mar 15;404:113-22. doi: 10.1016/j.mce.2015.01.037. Epub 2015 Jan 30.
The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion.
生物活性脂质鞘氨醇-1-磷酸（S1P）已成为癌细胞迁移和侵袭的强效诱导剂。此前，我们已表明S1P通过S1P受体1和3（S1P1,3）诱导ML-1滤泡性甲状腺癌细胞的侵袭。基质金属蛋白酶（MMPs）是锌依赖性蛋白水解酶，细胞在侵袭和迁移过程中利用它们降解细胞外基质。在本研究中，我们研究了MMP2和MMP9在S1P诱导的ML-1细胞侵袭中的作用，发现S1P通过S1P1,3调节MMP2和MMP9的分泌及活性。MMP2和MMP9的药理抑制剂及siRNA敲低均可减弱S1P诱导的侵袭。此外，我们表明钙蛋白酶和Rac1介导S1P诱导的MMP2和MMP9分泌。总之，MMP2和MMP9参与S1P诱发的滤泡性ML-1甲状腺癌细胞侵袭。
