Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis.
Overexpression of CTHRC1 in hepatocellular carcinoma promotes tumor invasion and predicts poor prognosis.
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DOI：
10.1371/journal.pone.0070324
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jeng YM
中科院分区：
文献类型：
--
作者：
Chen YL;Wang TH;Hsu HC;Yuan RH;Jeng YM
CTHRC 1是一种分泌型糖蛋白，激活Wnt信号传导的平面细胞极性途径。使用微阵列分析，我们发现CTHRC 1基因在肝细胞癌（HCC）中过表达。应用真实的时间反转录-聚合酶链反应（RT-PCR）检测201例手术切除的肝癌组织中CTHRC 1 mRNA的表达。CTHRC 1在HCC中的过表达与肿瘤大小和晚期肿瘤相关。此外，在多变量分析中，CTHRC 1的表达被确定为独立的预后因素。抑制CTHRC 1表达可抑制肿瘤的迁移和侵袭，而过表达CTHRC 1可促进肿瘤的侵袭。RhoA的激活，而不是Rac 1或Cdc 42，被发现在CTHRC 1诱导的细胞迁移中起着至关重要的作用。CTHRC 1通过诱导整合素β1表达和激活黏着斑激酶促进癌细胞与细胞外基质的粘附。这些结果表明CTHRC 1通过增强肿瘤细胞的粘附和迁移能力促进肿瘤的侵袭和转移。它也是一个有前途的生物标志物，用于预测肝癌患者的预后。
Collagen triple helix repeat containing-1 (CTHRC1) is a secreted glycoprotein that activates the planar cell polarity pathway of Wnt signaling. Using microarray analysis, we found that the CTHRC1 gene is overexpressed in hepatocellular carcinoma (HCC). The level of CTHRC1 mRNA was measured in 201 surgically resected HCCs using real time reverse transcription-polymerase chain reaction. Overexpression of CTHRC1 in HCC was associated with large tumor size and advanced tumor stage. Furthermore, expression of CTHRC1 as was identified as an independent prognostic factors in the multivariate analysis. Suppression of CTHRC1 expression inhibited tumor migration and invasion whereas overexpression of CTHRC1 promoted tumor invasion. Activation of RhoA, but not Rac1 or Cdc42, was found to play a crucial role in CTHRC1-induced cell migration. CTHRC1 promoted adhesion of cancer cells to extracellular matrix through induction of integrin β1 expression and activation of focal adhesion kinase. These results suggest CTHRC1 promotes tumor invasion and metastasis by enhancing the adhesion and migratory abilities of tumor cells. It is also a promising biomarker for predicting the prognosis of patients with HCC.
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影响因子：
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