Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma.

Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma.
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再生肝磷酸酶 3 (PRL-3) 与胃癌的转移和不良预后相关。

DOI:
10.1186/1479-5876-11-309
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发表时间:
2013-12-13
影响因子:
7.4
通讯作者:
Ji J
Ji J
中科院分区:
医学2区
文献类型:
--
作者:
Xing X;Lian S;Hu Y;Li Z;Zhang L;Wen X;Du H;Jia Y;Zheng Z;Meng L;Shou C;Ji J

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PRL-3是再生肝磷酸酶家族的成员之一,具有磷酸酶活性结构域和C-末端异戊烯基化基序。PRL-3的过表达与多种癌症有关。在这里,我们研究了PRL-3在胃癌中的临床意义以及利用不同结构突变体的转移生物学功能。采用免疫组化法检测196例胃癌和21例肝转移癌组织中PRL-3的表达。将一系列野生型PRL-3或其突变体质粒在BGC 823细胞中表达,以研究其催化活性、细胞定位和体外转移潜能之间的关系。PRL-3在胃癌组织中的阳性表达率为19.4%(38/196),在肝转移癌组织中的阳性表达率为76.2%(16/21)。PRL-3的表达与淋巴结转移、血管浸润密切相关(P < 0.05)。PRL-3高表达的患者5年总生存率较低(P = 0.011)。野生型PRL-3表达细胞的迁移和侵袭能力增强,而PRL-3(C104 S)或PRL-3(ΔCAAX)突变体的出现则使其迁移和侵袭能力大大减弱,并伴有其亚细胞定位的改变。转移相关蛋白PRL-3可能作为胃癌的一个潜在的预后生物标志物。磷酸酶催化活性和细胞定位对其功能至关重要。
PRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants. PRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro. Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P < 0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P = 0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(ΔCAAX) mutants accompanied with its alteration in subcellular localization. Metastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function.
PRL-3 通过 PRL-3-整合素 beta1-ERK1/2 和-MMP2 信号传导促进 LoVo 结肠癌细胞的运动、侵袭和转移。
DOI: 10.1186/1476-4598-8-110
发表时间: 2009-11-24
期刊: Molecular cancer
影响因子: 37.3
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发表时间: 2008-02-01
影响因子: 5.1
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发表时间: 2004-11-01
影响因子: 11.5
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DOI: 10.1126/science.1065817
发表时间: 2001-11-09
期刊: SCIENCE
影响因子: 56.9
作者:
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通讯作者: Vogelstein, B