Vinculin and filamin-C are two potential prognostic biomarkers and therapeutic targets for prostate cancer cell migration.

Jianzhong Ai,Tao Jin,Hong Li,Ye Zhu,Yang Yang,Lu Yang,Qiang Wei

doi:10.18632/oncotarget.19397

Abstract

Prostate cancer (PCa) is one of the most common diseases for male population, and the effective treatment for metastatic castration-resistant PCa is still lacking. To unravel the underlying mechanism of PCa cell migration, we plan to analyze the related crucial proteins and their roles. In our study, we firstly identify the differentially expressed proteins using quantitative proteomics, and confirm their mRNA expression using quantitative polymerase chain reaction (qPCR). The alterations of these proteins at DNA and mRNA levels are obtained from cBioPortal database. Furthermore, the functions of these proteins are evaluated using wound-healing assay. The quantitative proteomics identified vinculin (VCL) and filamin-C (FLNC) as two highly expressed proteins in PC3 cells, and the DNA and mRNA of these two proteins were amplified and upregulated in a part of PCa patients. Knockdown of VCL and FLNC gene expression significantly inhibit PCa cell migration. These findings suggest that VCL and FLNC identified by quantitative proteomics are highly expressed in PCa cells with high migration potential, and they could be effective targets for repressing PCa cell migration, paving a new avenue for the prognosis and treatment of advanced PCa.

Highlights

As we know, prostate cancer (PCa) is one of the most common malignancies among male population, it is the second most diagnosed malignancy and fifth leading cause of cancer-related death worldwide [1]
Knockdown of VCL and FLNC gene expression significantly inhibit Prostate cancer (PCa) cell migration. These findings suggest that VCL and FLNC identified by quantitative proteomics are highly expressed in PCa cells with high migration potential, and they could be effective targets for repressing PCa cell migration, paving a new avenue for the prognosis and treatment of advanced PCa
As per the bioinformatics analysis, two highly expressed proteins in PC3 cells, VCL and FLNC, were implied to play important roles in PCa cell migration (Figure 1A), and the mRNA expression of these two proteins was further confirmed by quantitative polymerase chain reaction (qPCR) (Figure 1B)

Summary

Introduction

Prostate cancer (PCa) is one of the most common malignancies among male population, it is the second most diagnosed malignancy and fifth leading cause of cancer-related death worldwide [1]. Several critical drugs were developed for the treatment of PCa, for advanced PCa, such as enzalutamide and abiraterone [2, 3]. The efficacy of these drugs were markedly limited by the relapse of PCa. Currently, the underlying mechanism for the relapse is still largely unknown. It is an effective way to inhibit the PCa progression by repressing its migration and metastasis. This study utilized the quantitative proteomics to unravel the crucial proteins tightly associated with the cancer cell migration

Methods

Results

Conclusion