SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway.
SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway.
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SPOCK1作为潜在的癌症预后标志物，通过激活PI3K/AKT通路促进胆囊癌细胞的增殖和转移。
DOI：
10.1186/s12943-014-0276-y
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发表时间：
2015-01-27
期刊：
影响因子：
37.3
通讯作者：
Liu YB
中科院分区：
文献类型：
--
作者：
Shu YJ;Weng H;Ye YY;Hu YP;Bao RF;Cao Y;Wang XA;Zhang F;Xiang SS;Li HF;Wu XS;Li ML;Jiang L;Lu W;Han BS;Jie ZG;Liu YB
胆囊癌（GBC）是全球癌症相关死亡的主要原因，其预后仍然很差，5年生存率约为5%。在这项研究中，我们分析了一种新的蛋白聚糖，Sparc/骨连接蛋白，cwcv和kazal样结构域蛋白聚糖1 （SPOCK1）在人类GBC肿瘤进展和预后中的作用。SPOCK1表达水平在新鲜样本和保存的GBC和邻近的非肿瘤组织样本中进行测量。通过细胞计数试剂盒-8、菌落形成、EdU保留实验、创面愈合和transwell迁移实验、流式细胞术分析、western blotting、裸鼠体内肿瘤发生和转移等方法探讨SPOCK1对细胞生长、DNA复制、迁移和侵袭的影响。与非肿瘤组织相比，人GBC组织中SPOCK1 mRNA和蛋白水平升高。免疫组织化学分析显示，与未发生转移的肿瘤相比，发生转移的肿瘤中SPOCK1水平升高，这与组织学分化和患者总生存期缩短显著相关。通过慢病毒介导的shRNA转导，敲低SPOCK1的表达，可显著抑制GBC细胞的生长、集落形成、DNA复制和体外侵袭。在裸鼠中，敲除细胞也形成了比对照GBC细胞更小的异种移植肿瘤。SPOCK1过表达则有相反的效果。此外，SPOCK1通过调控相关基因的表达，促进癌细胞迁移和上皮间质转化。我们发现PI3K/Akt通路的激活参与了SPOCK1在GBC中的致癌功能。SPOCK1激活PI3K/Akt信号通路，阻断GBC细胞凋亡，促进细胞增殖和转移。SPOCK1水平随着人GBC的进展而升高。SPOCK1作为一种致癌基因，可能是GBC患者的预后因素或治疗靶点。本文的在线版本（doi:10.1186/s12943-014-0276-y）包含补充材料，可供授权用户使用。
Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC. SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice. SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC. SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC. The online version of this article (doi:10.1186/s12943-014-0276-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.jamcollsurg.2010.09.009
发表时间：
2011-01-01
影响因子：
5.2
作者：
Butte, Jean M.;Matsuo, Kenichi;Jarnagin, William R.
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