Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2V 1P9, Canada.
Alberta Precision Laboratories, Calgary, AB T2V 1P9, Canada.
Int J Mol Sci. 2022 Jan 27;23(3):1476. doi: 10.3390/ijms23031476.
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 ( < 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.
ARPC1B（肌动蛋白相关蛋白 2/3 复合物亚基 1B）已被发现参与免疫介导的炎症性疾病和嗜酸性粒细胞增多症中的血小板异常。然而，其在前列腺癌（PCa）中的作用尚未确定。我们通过体外细胞模型和 PCa 临床数据，研究了 ARPC1B 在 PCa 侵袭和转移中的作用及其预后。与良性前列腺组织相比，局限性和去势抵抗性 PCa（CRPC）中 ARPC1B 的免疫组化（IHC）表达更高（<0.01）。此外，5 级（GG）患者中有 47%表现出高 ARPC1B 表达，而其他 GG 患者则表现出低 ARPC1B 表达。评估 ARPC1B 表达与 PCa 中两种常见遗传异常（ERG 和 PTEN）之间的关系表明，联合评估 ARPC1B 和 PTEN 以及 ARPC1B 和 ERG 与总生存和特定原因生存有显著关联。ARPC1B 的敲低通过下调 Aurora A 激酶（AURKA）损害了 PC3 和 DU145 PCa 细胞的迁移和侵袭，并导致细胞在细胞周期的 G2/M 检查点停滞。此外，与正常 PC3 相比，稳定的 PC3-ERG 细胞中观察到更高的 ARPC1B 表达，支持 ERG 与 ARPC1B 之间的关联。我们的研究结果表明，ARPC1B 在与 ERG 相关的 PCa 侵袭和转移中起作用，并进一步支持其作为生物标志物与 ERG 和 PTEN 相关的预后价值，以识别 PCa 癌症的侵袭性表型。
