Background

Disheveled-associated activator of morphogenesis (DAAM) family, including DAAM1 and DAAM2, is key regulators in Wnt signaling pathway. Although the oncogenic role of Wnt signaling pathway in colorectal cancer (CRC) was investigated in several lines, the expression and function of DAAM in CRC are still obscure.

Objective

To investigate the expression and function of DAAM in CRC.

Methods

DAAM1 and DAAM2 expression in high grade dysplasia (HGD), CRCs and corresponding adjacent tissues were detected with qRT-PCR and immunohistochemistry (IHC). The prognostic significance of DAAM1/2 were estimated with univariate and multivariate analyses. Moreover, the correlations between clinicopathological factors and DAAM were evaluated with the χ² test. With experiments in vitro, we investigated the function of DAAM2 in CRC cell proliferation and invasion, and investigated the underlying mechanism of how DAAM2 facilitated CRC invasion.

Results

DAAM2, instead of DAAM1, was substantially up-regulated in CRCs compared with paired adjacent normal tissues and HGDs. The ratio of high DAAM1 and DAAM2 expression accounted for 44.83% and 46.31%, respectively. High DAAM2, instead of DAAM1, was a risk factor indicating an unfavorable prognosis of CRC. In multivariate analysis, high DAAM2 was identified as an independent prognostic biomarker of CRC predicting poor prognosis. With experiments in vitro, DAAM2 promoted invasion of CRC cells via activating PAK1 and promoting the expression of MMP7, suggesting an essential role of DAAM2 in CRC invasion.

Conclusions

High expression of DAAM2, instead of DAAM1, indicated an unfavorable prognosis of CRC independently, which suggested that detecting DAAM2 can help define the high-risk patients. DAAM2 activated PAK1 and promoted MMP7 expression and facilitated the invasion of CRC cells, indicating that DAAM2 may be a potential drug target of CRC.

中文翻译：

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形态发生的蓬乱相关激活剂2通过激活PAK1和促进MMP7表达促进结直肠癌的侵袭

背景

蓬乱相关的形态发生激活因子 (DAAM) 家族，包括 DAAM1 和 DAAM2，是 Wnt 信号通路中的关键调节因子。尽管 Wnt 信号通路在结直肠癌 (CRC) 中的致癌作用已在多个方面进行了研究，但 DAAM 在结直肠癌中的表达和功能仍不清楚。

客观的

探讨DAAM在CRC中的表达和功能。

方法

用 qRT-PCR 和免疫组织化学 (IHC) 检测 DAAM1 和 DAAM2 在高度不典型增生 (HGD)、CRC 和相应的邻近组织中的表达。通过单变量和多变量分析估计 DAAM1/2 的预后意义。此外，临床病理因素与DAAM的相关性采用χ ²检验。通过体外实验，我们研究了 DAAM2 在 CRC 细胞增殖和侵袭中的作用，并研究了 DAAM2 如何促进 CRC 侵袭的潜在机制。

结果

与配对的相邻正常组织和 HGD 相比，在 CRC 中 DAAM2 而非 DAAM1 显着上调。DAAM1和DAAM2高表达的比例分别占44.83%和46.31%。高 DAAM2 而非 DAAM1 是指示 CRC 预后不良的危险因素。在多变量分析中，高 DAAM2 被确定为 CRC 预测不良预后的独立预后生物标志物。通过体外实验，DAAM2通过激活PAK1和促进MMP7的表达来促进CRC细胞的侵袭，提示DAAM2在CRC侵袭中的重要作用。

结论

DAAM2 而非 DAAM1 的高表达独立表明 CRC 的不良预后，这表明检测 DAAM2 有助于确定高危患者。DAAM2 激活 PAK1 并促进 MMP7 表达并促进 CRC 细胞的侵袭，表明 DAAM2 可能是 CRC 的潜在药物靶点。