Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling.
Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling.
复制标题
磷脂酶 C delta 1 通过调节 KIF3A 介导的 ERK1/2/β-catenin/MMP7 信号传导抑制乳腺癌细胞的细胞迁移和侵袭
DOI：
10.18632/oncotarget.16072
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Ren G
中科院分区：
文献类型：
--
作者：
Shao Q;Luo X;Yang D;Wang C;Cheng Q;Xiang T;Ren G
磷脂酶C δ1 （PLCD1）编码一种参与能量代谢、钙稳态和细胞内运动的酶。它位于3p22的一个在多种癌症中经常被删除的区域，PLCD1酶是乳腺癌中抑制基质金属蛋白酶（MMP）的潜在肿瘤抑制因子7，但其详细机制尚不清楚。在本研究中，我们发现PLCD1在乳腺癌中下调，并且通过功能增益或损失实验发现，PLCD1在体外通过ERK1/2/β-catenin/MMP7信号通路抑制细胞迁移和侵袭。此外，KIF3A被鉴定为PLCD1的下游介质，PLCD1与KIF3A的表达呈负相关。单独敲低KIF3A表达可抑制细胞迁移和侵袭，并减弱通过敲低PLCD1而重新激活的ERK1/2/β-catenin/MMP7信号。总的来说，我们的研究结果表明，PLCD1通过kif3a介导的ERK1/2/β-catenin/MMP7信号的抑制，至少部分地在乳腺癌中起肿瘤抑制作用。
Phospholipase C δ1 (PLCD1) encodes an enzyme involved in energy metabolism, calcium homeostasis and intracellular movement. It is located at 3p22 in a region that is frequently deleted in multiple cancers, and the PLCD1 enzyme is a potential tumour suppressor in breast cancer that inhibits matrix metalloprotease (MMP) 7, but the detailed mechanism remains elusive. In this study, we found that PLCD1 was downregulated in breast cancers, and the gain-or-loss functional assay revealed that PLCD1 inhibited cell migration and invasion in vitro via the ERK1/2/β-catenin/MMP7 signalling pathway. Furthermore, KIF3A was identified as a downstream mediator of PLCD1, and there was an inverse correlation between the expression of PLCD1 and KIF3A. Knockdown of KIF3A expression alone suppressed cell migration and invasion, and attenuated ERK1/2/β-catenin/MMP7 signalling that was reactivated by knocking down PLCD1 in vitro. Collectively, our findings suggest that PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of ERK1/2/β-catenin/MMP7 signalling, at least in part, in breast cancer.