ARPC1B Is Associated with Lethal Prostate Cancer and Its Inhibition Decreases Cell Invasion and Migration In Vitro.

Yaser Gamallat,Konstantinos Liosis,Hend Zaaluk,Sunita Ghosh,Ramy Abdelsalam,Ealia Khosh Kish,Tarek A Bismar

doi:10.3390/ijms23031476

Yaser Gamallat, Konstantinos Liosis + Show 5 more

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https://doi.org/10.3390/ijms23031476

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Abstract

ARPC1B (Actin Related Protein 2/3 Complex Subunit 1B) has been found to be involved in platelet abnormalities of immune-mediated inflammatory disease and eosinophilia. However, its role in prostate cancer (PCa) has not been established. We characterized the role of ARPC1B in PCa invasion and metastasis and investigated its prognosis using in vitro cellular models and PCa clinical data. Higher immunohistochemistry (IHC) expressions of ARPC1B were observed in localized and castrate resistant PCa (CRPC) vs. benign prostate tissue (p < 0.01). Additionally, 47% of patients with grade group 5 (GG) showed high ARPC1B expression vs. other GG patients. Assessing ARPC1B expression in association with two of the common genetic aberrations in PCa (ERG and PTEN) showed significant association to overall and cause-specific survival for combined assessment of ARPC1B and PTEN, and ARPC1B and ERG. Knockdown of ARPC1B impaired the migration and invasion of PC3 and DU145 PCa cells via downregulation of Aurora A kinase (AURKA) and resulted in the arrest of the cells in the G2/M checkpoint of the cell cycle. Additionally, higher ARPC1B expression was observed in stable PC3-ERG cells compared to normal PC3, supporting the association between ERG and ARPC1B. Our findings implicate the role of ARPC1B in PCa invasion and metastasis in association with ERG and further support its prognostic value as a biomarker in association with ERG and PTEN in identifying aggressive phenotypes of PCa cancer.

Highlights

Prostate cancer (PCa) is, worldwide, the most common type of cancer among men [1].identifying molecular biomarkers related to prostate cancer (PCa) progression and patient prognosis remains an important topic in cancer research
There was an increase in expression of the ARPC1B in castration-resistant prostate cancer (CRPC), and localized PCa compared with benign prostate tissue through the IHC Figure 1
The degree of downregulation of those markers was lower in PC3-ERG compared to PC3 cells

Summary

Introduction

Prostate cancer (PCa) is, worldwide, the most common type of cancer among men [1]. Identifying molecular biomarkers related to PCa progression and patient prognosis remains an important topic in cancer research. The actin-related protein 2/3 complex subunit 1B(ARPC1B) gene is one of the seven actin cytoskeleton subunits of the human Arp2/3 protein complex [2]. The Arp2/3 protein complex includes the actin-related ARPC1, which contains the two ARPC1A and ARPC1B isoforms, ARP2, ARP3, ARPC2, ARPC3, ARPC4, and ARPC5 [3]. This complex appears to be an essential part of most eukaryotic cells because it directly regulates cell motility [4]

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