PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells.

Takuya Yoshimura,Sohsuke Yamada,Masato Tsutsui,Taiji Hamada,Kazuhito Hatanaka,Akihide Tanimoto,Norifumi Nakamura,Takako Yoshioka,Hiroshi Hijioka,Yoshihisa Umekita,Masakazu Souda

doi:10.18632/oncotarget.7529

Abstract

Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia-like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death.

Highlights

Purkinje cell protein (PCP) 4, known as peptide (PEP) 19, was first identified in rat cerebellum as a polypeptide of 7.6 kDa that shows homology to the calcium binding β-chain of the S100 protein [1]
The number of filopodia-like cytoplasmic projections per cell were decreased in Bmi-1 and PCP4/PEP19 knockdown cells (Figure 2A), and imuunocytochemical analysis of vinculin expression showed rod- or spot-like structures within cytoplasmic processes (Figure 2B) corresponding to focal adhesion complexes, which were decreased in number (Figure 3A and 3B)
PCP4/PEP19 has an anti-apoptotic function in human breast cancer cell lines [16]

Summary

Introduction

Purkinje cell protein (PCP) 4, known as peptide (PEP) 19, was first identified in rat cerebellum as a polypeptide of 7.6 kDa that shows homology to the calcium binding β-chain of the S100 protein [1]. It is expressed in Purkinje cells and stellate neurons [2] and binds calmodulin (CaM), thereby regulating CaMdependent signaling [3,4,5] by modulating calcium/ CaM-dependent protein kinase (CaMK) activity [6, 7] to influence a variety of processes in neurons, including apoptosis [8,9,10,11]. We detected PCP4/PEP19 expression in human breast cancer and found that it exerts antiapoptotic functions in human breast cancer cell lines via CaMKK and Akt signaling pathways [16]

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Conclusion