Protocadherin 7 is overexpressed in castration resistant prostate cancer and promotes aberrant MEK and AKT signaling.
Protocadherin 7 is overexpressed in castration resistant prostate cancer and promotes aberrant MEK and AKT signaling.
复制标题
原钙粘蛋白 7 在去势抵抗性前列腺癌中过度表达，并促进异常的 MEK 和 AKT 信号传导。
DOI：
10.1002/pros.23898
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Koul,HariK
中科院分区：
文献类型：
--
作者：
Shishodia,Gauri;Koul,Sweaty;Koul,HariK
背景去势抵抗性前列腺癌（CRPC）几乎是所有前列腺癌（PCa）死亡的原因. ERK/MEK和PI 3 K/AKT信号通路的异常激活在CRPC患者亚群中起重要作用。本研究首次在PCa中研究了原钙粘蛋白7（PCDH 7）在这些信号通路中的作用。通过Western印迹和免疫组织化学评估蛋白质表达，通过定量真实的时间聚合酶链反应评估信使RNA（mRNA）。使用小发夹核糖核酸敲低PCDH 7。结果在CRPC/NEPC数据集中，41%的患者PCDH 7扩增/mRNA表达上调。PCDH 7在CRPC细胞中也过表达。在PCa组织和TRAMP小鼠的肿瘤进展过程中观察到PCDH蛋白表达增加。表皮生长因子处理导致ERK/AKT的异常激活。敲低PCDH 7降低ERK，AKT和RB磷酸化和减少集落形成，减少细胞侵袭，和cellmigration.ConclusionsThese数据首次显示，PCDH 7是过度表达在大量的CRPC患者，并建议PCDH 7可能是一个有吸引力的目标，在CRPC患者的子集，其中有没有治愈的日期。
BackgroundCastrate resistant prostate cancer (CRPC) accounts for almost all prostate cancer (PCa) deaths. Aberrant activation of ERK/MEK and PI3K/AKT signaling pathways plays an important role in subsets of patients with CRPC. The role of protocadherin 7 (PCDH7) in modulating these signaling pathways is investigated for the first time in PCa in the present investigation.MethodsPCDH7 expression was analyzed in CRPC/neuroendocrine prostate cancer (NEPC) dataset. Protein expression was assessed by Western blotting and immunohistochemistry, and messenger RNA (mRNA) by quantitative real‐time polymerase chain reaction. Small hairpin ribonucleic acid was used to knockdown PCDH7. Colony formation, cell migration, and invasion studies were done using standard protocols.ResultsPCDH7 amplification/mRNA upregulation was observed in 41% of patients in CRPC/NEPC dataset. PCDH7 was also overexpressed in CRPC cells. Increased PCDH protein expression was observed during tumor progression in PCa tissues and in TRAMP mice. Epidermal growth factor treatment resulted in aberrant activation of ERK/AKT. Knockdown of PCDH7 decreased ERK, AKT, and RB phosphorylation and reduced colony formation, decreased cell invasion, and cell migration.ConclusionsThese data show for the first time that PCDH7 is overexpressed in a large number of patients with CRPC and suggest that PCDH7 may be an attractive target in subsets of patients with CRPC for whom there is no cure to‐date.