Shao Qing, Luo Xinrong, Yang Dejuan, Wang Can, Cheng Qiao, Xiang Tingxiu, Ren Guosheng
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Oncotarget. 2017 Apr 25;8(17):29056-29066. doi: 10.18632/oncotarget.16072.
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.
磷脂酶Cδ1（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，该区域在多种癌症中经常缺失，并且PLCD1酶是乳腺癌中一种潜在的肿瘤抑制因子，可抑制基质金属蛋白酶（MMP）7，但具体机制仍不清楚。在本研究中，我们发现PLCD1在乳腺癌中表达下调，功能获得或缺失实验表明PLCD1通过ERK1/2/β-连环蛋白/MMP7信号通路在体外抑制细胞迁移和侵袭。此外，KIF3A被鉴定为PLCD1的下游介质，并且PLCD1和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，并减弱在体外敲低PLCD1后重新激活的ERK1/2/β-连环蛋白/MMP7信号。总的来说，我们的研究结果表明，至少在部分乳腺癌中，PLCD1通过KIF3A介导的ERK1/2/β-连环蛋白/MMP7信号抑制发挥肿瘤抑制作用。
