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KMID : 0381120210430080923
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Genes and Genomics
2021 Volume.43 No. 8 p.923 ~ p.935
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Disheveled-associated activator of morphogenesis 2 promotes invasion of colorectal cancer by activating PAK1 and promoting MMP7 expression
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Chen Aimei
Liu Zhiqiang
Wu Quanyan
Li Hailin
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Abstract
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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.
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KEYWORD
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Disheveled-associated activator of morphogenesis 2, PAK1, Colorectal cancer, Invasion, Prognosis
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