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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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Abstract

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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Authors and Affiliations

  1. Department of Chinese Traditional Medicine, Weifang Yidu Central Hospital, Weifang, 262500, Shandong, China

    Aimei Chen, Zhiqiang Liu & Quanyan Wu

  2. Department of General Surgery, Qilu Hospital of Shandong University, #107 Wenhua Road, Jinan, 250012, Shandong, China

    Hailin Li

Authors
  1. Aimei Chen
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  2. Zhiqiang Liu
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  3. Quanyan Wu
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  4. Hailin Li
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Contributions

AC, and ZL performed the experiments, QW, and HL collected the specimens. HL designed the study and wrote the paper.

Corresponding author

Correspondence to Hailin Li.

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Author Aimei Chen, Zhiqiang Liu, Quanyan Wu, and Hailin Li declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of Weifang Yidu Central Hospital, Qilu Hospital of Shandong University with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Chen, A., Liu, Z., Wu, Q. et al. Disheveled-associated activator of morphogenesis 2 promotes invasion of colorectal cancer by activating PAK1 and promoting MMP7 expression. Genes Genom 43, 923–935 (2021). https://doi.org/10.1007/s13258-021-01111-1

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  • DOI: https://doi.org/10.1007/s13258-021-01111-1

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