Lee So Hee, Paek A Rome, Yoon Kyungsil, Kim Seok Hyun, Lee Soo Young, You Hye Jin
Cancer Cell and Molecular Biology Branch, Div. of Cancer Biology, National Cancer Center, Goyang 410-769; Division of Molecular Life Sciences, Ewha Womans University, Seoul 120-750, Korea.
Cancer Cell and Molecular Biology Branch, Div. of Cancer Biology, National Cancer Center, Goyang 410-769, Korea.
BMB Rep. 2015 Feb;48(2):115-20. doi: 10.5483/bmbrep.2015.48.2.035.
Tight junction protein 1 (TJP1), a component of tight junction, has been reported to play a role in protein networks as an adaptor protein, and TJP1 expression is altered during tumor development. Here, we found that TJP1 expression was increased at the RNA and protein levels in TGF-β-stimulated lung cancer cells, A549. SB431542, a type-I TGF-β receptor inhibitor, as well as SB203580, a p38 kinase inhibitor, significantly abrogated the effect of TGF-β on TJP1 expression. Diphenyleneiodonium, an NADPH oxidase inhibitor, also attenuated TJP1 expression in response to TGF-β in lung cancer cells. When TJP1 expression was reduced by shRNA lentiviral particles in A549 cells (A549-sh TJP1), wound healing was much lower than in cells infected with control viral particles. Taken together, these data suggest that TGF-β enhances TJP1 expression, which may play a role beyond structural support in tight junctions during cancer development.
紧密连接蛋白1（TJP1）是紧密连接的一个组成部分，据报道它作为一种衔接蛋白在蛋白质网络中发挥作用，并且TJP1的表达在肿瘤发展过程中会发生改变。在此，我们发现，在经转化生长因子-β（TGF-β）刺激的肺癌细胞A549中，TJP1在RNA和蛋白质水平上的表达均有所增加。I型TGF-β受体抑制剂SB431542以及p38激酶抑制剂SB203580均显著消除了TGF-β对TJP1表达的影响。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂二亚苯基碘鎓也减弱了肺癌细胞中TGF-β诱导的TJP1表达。当通过短发夹RNA（shRNA）慢病毒颗粒降低A549细胞（A549-sh TJP1）中的TJP1表达时，伤口愈合能力远低于感染对照病毒颗粒的细胞。综上所述，这些数据表明TGF-β增强了TJP1的表达，这在癌症发展过程中可能在紧密连接中发挥超出结构支持的作用。
