Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China; Institude of Urology, The First Hospital of China Medical University, Shenyang, 110001, China.
Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China; Institude of Urology, The First Hospital of China Medical University, Shenyang, 110001, China.
Biochem Biophys Res Commun. 2018 Jul 2;501(4):913-919. doi: 10.1016/j.bbrc.2018.05.081. Epub 2018 May 21.
Transforming growth factor-β1 (TGF-β1) plays a crucial role in the signaling network that controls cellular invasion and motility capability during tumor development. To investigate whether fascin1 plays a crucial role in TGF-β1-facilitated invasion and migration of kidney cancer cells (KCC), real-time PCR and western blotting were used to test the fascin1 expression after TGF-β1 treatment (10 ng/ml) in 769-P and OSRC cells. Fascin1 was silenced using the small interfering RNA (siRNA) technique. Cytoskeleton staining was used to test the change of Cytoskeleton. Cell migration and invasion changes were measured by wound-healing and Transwell assay. The results indicate that mRNA and protein levels of fascin1 were dramatically increased after treatment with 10 ng/ml TGF-β1 in 769-P and OSRC cells. TGF-β1 promoted the occurrence of EMT (Epithelial-Mesenchymal Transition) and the invasive and migratory capabilities of the two cell lines after treatment with 10 ng/ml TGF-β1. In addition, fascin1 siRNA dramatically attenuated the invasiveness and migration induced by TGF-β1. Furthermore, we identified that specific inhibitors of ERK and JNK signaling pathways, FR180204 and SP600125, can suppress TGF-β1-induced fascin1 expression. In conclusion, these results reveal that fascin1 is an important mediator of TGF-β1-induced invasion and migration of KCC through ERK and JNK signal pathways.
转化生长因子-β1（TGF-β1）在信号网络中起着至关重要的作用，该信号网络控制着肿瘤发展过程中细胞的侵袭和运动能力。为了研究 fascin1 是否在 TGF-β1 促进肾癌细胞（KCC）侵袭和迁移中起关键作用，我们使用实时 PCR 和 Western blot 检测了 TGF-β1（10ng/ml）处理后 769-P 和 OSRC 细胞中 fascin1 的表达。使用小干扰 RNA（siRNA）技术沉默 fascin1。细胞骨架染色用于检测细胞骨架的变化。通过划痕愈合和 Transwell 测定测量细胞迁移和侵袭的变化。结果表明，在 769-P 和 OSRC 细胞中，10ng/ml TGF-β1 处理后 fascin1 的 mRNA 和蛋白水平显著增加。TGF-β1 促进了 EMT（上皮-间充质转化）的发生，以及这两种细胞系在 10ng/ml TGF-β1 处理后的侵袭和迁移能力。此外，fascin1 siRNA 显著减弱了 TGF-β1 诱导的侵袭和迁移。此外，我们发现 ERK 和 JNK 信号通路的特异性抑制剂 FR180204 和 SP600125 可以抑制 TGF-β1 诱导的 fascin1 表达。总之，这些结果表明 fascin1 是 TGF-β1 通过 ERK 和 JNK 信号通路诱导 KCC 侵袭和迁移的重要介质。
