Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells

Dai,Bin; Shen,Yucheng; Yan,Ting; Zhang,Ailiang

doi:10.3892/or.2019.7424

Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells

Authors:
- Bin Dai
- Yucheng Shen
- Ting Yan
- Ailiang Zhang
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Affiliations: Department of Orthopedics, Binhai County People's Hospital, Binhai, Jiangsu 224500, P.R. China, Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China, Department of Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China
Published online on: December 10, 2019 https://doi.org/10.3892/or.2019.7424
Pages: 601-608

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Abstract

Receptor tyrosine kinase like orphan receptor 2 (ROR2) regulates Wnt5a-induced cell migration by phosphorylating PI3K/Akt and activating RhoA in osteosarcoma. However, the role of Wnt5a signaling and its corresponding receptors in the regulation of osteosarcoma metastasis remains poorly understood. ROR1 monoclonal antibody (mAb) and short hairpin (sh)RNA targeting ROR2 markedly inhibited the activity of dishevelled associated activator of morphogenesis 1 (DAAM1) and RhoA and retarded cell migration in osteosarcoma. ROR1 mAb and ROR2 shRNA destroyed the microfilament formation of osteosarcoma cells. Silencing of DAAM1 (with DAAM1 shRNA) downregulated RhoA activity and inhibited cell migration. The decrease of cell migration caused by DAAM1 shRNA was rescued by wild-type DAAM1 overexpression. DAAM1 and PI3Kα/Akt were parallel signaling pathways mediating osteosarcoma cell migration in response to Wnt5a. It was concluded that Wnt5a promotes osteosarcoma cell migration via ROR1/2 receptors, and then activates DAAM1 and RhoA.

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