Ouanouki Amira, Lamy Sylvie, Annabi Borhane
Laboratoire d'Oncologie Moléculaire, Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8.
Oncotarget. 2018 Apr 24;9(31):22023-22037. doi: 10.18632/oncotarget.25153.
Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-β-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration. The effects of anthocyanidins, the most abundant diet-derived flavonoids, were examined on periostin-mediated downstream signaling pathways. Anthocyanidins were found to decrease periostin expression whether added under pre-, co- or post-treatment conditions along with TGF-β, and altered the Akt and Fak signaling pathways. These effects were similar to Galunisertib (LY2157299), a small molecule inhibitor of the TGF-β receptor I kinase. Taken together, our data demonstrate that periostin acts as a central element in TGF-β-induced EMT, which can be prevented by diet-derived anthocyanidins.
骨膜蛋白是一种分泌蛋白，与正常脑组织相比，其在胶质母细胞瘤细胞中高表达，因此被认为是治疗方式中的一种潜在生物标志物。然而，其在癌细胞侵袭表型中的作用尚不清楚。这项研究调查了骨膜蛋白在U-87 MG胶质母细胞瘤细胞侵袭、细胞迁移以及转化生长因子β（TGF-β）诱导的上皮-间质转化（EMT）中的作用。使用小干扰RNA使骨膜蛋白基因沉默，部分通过降低Smad2、Akt和Fak磷酸化以及U-87 MG细胞侵袭和迁移，减少了TGF-β诱导的纤连蛋白和波形蛋白等间质标志物的表达。研究了最丰富的膳食来源类黄酮花青素对骨膜蛋白介导的下游信号通路的影响。发现花青素无论在TGF-β处理前、处理期间还是处理后添加，均能降低骨膜蛋白表达，并改变Akt和Fak信号通路。这些作用与TGF-β受体I激酶的小分子抑制剂加仑替尼（LY2157299）相似。综上所述，我们的数据表明骨膜蛋白在TGF-β诱导的EMT中起核心作用，而膳食来源的花青素可以阻止这种作用。
