Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Liu,Guiyang; Yan,Ting; Li,Xiaorong; Sun,Jianhui; Zhang,Bo; Wang,Hongjie; Zhu,Yichao

doi:10.3892/or.2017.6124

Daam1 activates RhoA to regulate Wnt5a‑induced glioblastoma cell invasion

Authors:
- Guiyang Liu
- Ting Yan
- Xiaorong Li
- Jianhui Sun
- Bo Zhang
- Hongjie Wang
- Yichao Zhu
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Affiliations: Department of Neurosurgery, Jinan Fourth People's Hospital, Jinan, Shandong 250031, P.R. China, Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drugs of Jiangsu Province, School of Public Health, Nanjing, Jiangsu 211166, P.R. China, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
Published online on: December 1, 2017 https://doi.org/10.3892/or.2017.6124
Pages: 465-472
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The signaling pathway of dishevelled-associated activator of morphogenesis 1 (Daam1) triggered by Wnt5a drives cell movement and migration during breast cancer metastasis. However, Wnt5a signaling in glioblastoma progression remains poorly defined. Wnt5a expression and activations of RhoA, Cdc42, and Rac1 were detected in human glioblastoma tissues by using ELISA assays and small G-protein activation assays, respectively. The cell invasion rate and Daam1 activation of glioblastoma U251 and T98MG cells were determined by cell invasion assays and pull-down assays, respectively. According to our experiments, Wnt5a expression and RhoA activation were upregulated in invasive glioblastoma tissues, with a significant positive correlation between them. Wnt5a activated Daam1 and RhoA, and subsequently promoted the invasion of glioblastoma U251 and T98MG cells. This process was abolished by secreted frizzled-related protein 2 (sFRP2), an antagonist that directly binds to Wnt5a. Specific small interfering RNA (siRNA) targeting Daam1 markedly inhibited Wnt5a-induced RhoA activation, stress fiber formation and glioblastoma cell invasion. CCG-1423, a RhoA inhibitor, decreased Wnt5a-induced stress fiber formation and glioblastoma cell invasion. Finally, siRNA targeting Daam1 or CCG-1423 treatment did not alter the cell proliferation of glioblastoma U251 and T98MG cells. We thus concluded that Wnt5a promoted glioblastoma cell invasion via Daam1/RhoA signaling pathway.

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