TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.
TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.
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TPX2 是结肠癌生长和转移的新型预后标志物。
DOI：
10.1186/1479-5876-11-313
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发表时间：
2013-12-17
影响因子：
7.4
通讯作者：
Cai S
中科院分区：
文献类型：
--
作者：
Wei P;Zhang N;Xu Y;Li X;Shi D;Wang Y;Li D;Cai S
我们之前使用全基因组基因表达谱分析证明了微管相关蛋白TPX2在结肠癌中的异常过表达。本研究旨在探讨其在结肠癌中的表达模式、临床意义及生物学功能。分析了TPX2在人结肠癌细胞系和肿瘤标本中的表达。在体外和体内研究TPX2对细胞增殖、肿瘤发生和转移的影响。203例结肠癌转移灶中有129例（60.8%）TPX2过表达，显著高于原发癌组织和正常结肠黏膜。TPX2过表达与临床分期、血管侵袭和转移有显著相关性。在生存分析中，TPX2过表达患者的总生存期和无转移生存期较差，提示TPX2的失调可能有助于结肠癌的转移。与此一致的是，抑制TPX2的表达在体内和体外都能抑制结肠癌细胞的增殖和致瘤性。引人注目的是，我们发现TPX2敲低显著降低了结肠癌细胞的迁移和侵袭能力，这进一步证明了与akt介导的MMP2活性的机制相关。这些发现表明TPX2在促进人类结肠癌的发生和转移中起着重要作用，可能是一种新的预后生物标志物和治疗靶点。
We have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer. TPX2 expression was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo. TPX2 was overexpressed in 129 of the 203 (60.8%) colon cancer metastatic lesions, with the expression being significantly higher than that in primary cancerous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with clinical staging, vessel invasion, and metastasis. In survival analyses, patients with TPX2 overexpression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistent with this, suppression of TPX2 expression inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT-mediated MMP2 activity. These findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease.
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人类TPX2是将极光-A激酶靶向纺锤体所必需的。
影响因子：
7.8
作者：
Kufer, Thomas A;Sillje, Herman H W;Korner, Roman;Gruss, Oliver J;Meraldi, Patrick;Nigg, Erich A
通讯作者：
Nigg, Erich A
影响因子：
11.8
作者：
Özlü, N;Srayko, M;Hyman, AA
通讯作者：
Hyman, AA
影响因子：
11.5
作者：
Ma, Y;Lin, DM;Gao, YN
通讯作者：
Gao, YN
影响因子：
8
作者：
Cheng, J. C-H;Chou, C. H.;Hsieh, C-Y
通讯作者：
Hsieh, C-Y
影响因子：
64.5
作者：
Gruss, OJ;Carazo-Salas, RE;Mattaj, IW
通讯作者：
Mattaj, IW