标题:Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells
作者:Liu, Xiaofei; Zhang, Nianzhao; Wang, Dawei; Zhu, Deyu; Yuan, Quan; Zhang, Xiulei; Qian, Lilin; Niu, Huanmin; Lu, Yi; Ren, Guijie; 更多
作者机构:[Liu, Xiaofei; Wang, Dawei; Zhu, Deyu; Yuan, Quan; Zhang, Xiulei; Qian, Lilin; Niu, Huanmin; Lu, Yi; Ren, Guijie; Tian, Keli; Yuan, Huiqing] Shandong 更多
通讯作者:Tian, KL;Yuan, HQ
通讯作者地址:[Tian, KL; Yuan, HQ]Shandong Univ, Dept Biochem & Mol Biol, Sch Med, Jinan, Shandong, Peoples R China.
来源:CANCER SCIENCE
出版年:2018
卷:109
期:4
页码:1147-1157
DOI:10.1111/cas.13541
关键词:apoptosis; endoplasmic reticulum; necroptosis; prostate cancer;; reticulocalbin 1
摘要:Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+-binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2 in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal-based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis inresponse to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.
收录类别:SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044617783&doi=10.1111%2fcas.13541&partnerID=40&md5=0cdeb2e78125398742f7933cedaeb3d1
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