TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway.
TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway.
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TIMP1是通过FAK-PI3K/AKT和MAPK通路预测结肠癌进展和转移的预后标志物。
DOI：
10.1186/s13046-016-0427-7
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Song G;Xu S;Zhang H;Wang Y;Xiao C;Jiang T;Wu L;Zhang T;Sun X;Zhong L;Zhou C;Wang Z;Peng Z;Chen J;Wang X
组织抑制因子基质金属蛋白酶1(TIMP1)在肿瘤发生中起重要作用，但其确切的功能作用和调控尚不清楚。本研究旨在探讨其在人结肠癌中的生物学功能及其临床意义。我们分析了TIMP1在公共数据库(Oncomine和TCGA)以及94例原发结肠癌和配对的正常结肠组织标本中的表达。在体外和体内研究了TIMP1表达改变对细胞肿瘤发生、增殖和转移的潜在机制。TIMP1在结肠癌组织和淋巴结转移组织中的表达均高于正常组织。TIMP 1的异常表达与区域淋巴结转移(p = 0.033)、远处转移(p = 0.039)、血管侵犯(p = 0.024)和美国癌症联合委员会分期(p = 0.026)显著相关。COX比例风险模型显示，TIMP1是影响结肠癌患者无瘤生存期(HR = 2.603，95%CI：1.115-6.077，p = 0.027)和总生存期(HR = 2.907，95%CI：1.254-6.737，p = 0.013)的独立预后指标。与此一致，我们的研究结果表明，抑制TIMP1的表达可以通过诱导TIMP1特异性调节的FAK-PI3K/AKT和MAPK通路来抑制细胞的增殖和转移，但增加细胞的凋亡。TIMP1可能在促进结肠癌的发生和转移中发挥重要作用，并可作为结肠癌潜在的预后指标。本文的在线版本(doi：10.1186/s13046-0160427-7)包含补充材料，授权用户可以使用。
Tissue inhibitor matrix metalloproteinase 1 (TIMP1) plays a vital role in carcinogenesis, yet its precise functional roles and regulation remain unclear. In this study, we aim to investigate its biological function and clinical significance in human colon cancer. We analyzed the expression of TIMP1 in both public database (Oncomine and TCGA) and 94 cases of primary colon cancer and matched normal colon tissue specimens. The underlying mechanisms of altered TIMP1 expression on cell tumorigenesis, proliferation, and metastasis were explored in vitro and in vivo. TIMP1 was overexpressed in colon tumorous tissues and lymph node metastasis specimens than in normal tissues. The aberrant expression of TIMP1 was significantly associated with the regional lymph node metastasis (p = 0.033), distant metastasis (p = 0.039), vascular invasion (p = 0.024) and the American Joint Committee on Cancer (AJCC) stage (p = 0.026). Cox proportional hazards model showed that TIMP1 was an independent prognostic indicator of disease-free survival (HR = 2.603, 95 % CI: 1.115–6.077, p = 0.027) and overall survival (HR = 2.907, 95 % CI: 1.254–6.737, p = 0.013) for patients with colon cancer. Consistent with this, our findings highlight that suppression of TIMP1 expression decreased proliferation, and metastasis but increased apoptosis by inducing TIMP1 specific regulated FAK-PI3K/AKT and MAPK pathway. TIMP1 might play an important role in promoting tumorigenesis and metastasis of human colon cancer and function as a potential prognostic indicator for colon cancer. The online version of this article (doi:10.1186/s13046-016-0427-7) contains supplementary material, which is available to authorized users.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
50.3
作者：
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影响因子：
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通讯作者：
Ramont L
影响因子：
3.9
作者：
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