Phospholipase Cδ1 Suppresses Cell Migration and Invasion of Breast Cancer Cells by Modulating KIF3A-mediated ERK1/2/β- Catenin/MMP7 Signalling

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Apr 21

PMID 28423710

Citations 19

Authors

Qing Shao

Xinrong Luo

Dejuan Yang

Can Wang

Qiao Cheng

Tingxiu Xiang

Guosheng Ren

Affiliations

Soon will be listed here.

Abstract

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.

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