Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells
Wnt5a/ROR1 activates DAAM1 and promotes the migration in osteosarcoma cells
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DOI：
10.3892/or.2019.7424
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发表时间：
2020-02-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Ailiang
中科院分区：
文献类型：
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作者：
Dai, Bin;Shen, Yucheng;Zhang, Ailiang
受体酪氨酸激酶样孤儿受体2 （ROR2）在骨肉瘤中通过磷酸化PI3K/Akt和激活RhoA调控wnt5a诱导的细胞迁移。然而，Wnt5a信号及其相应受体在骨肉瘤转移调控中的作用尚不清楚。ROR1单克隆抗体（mAb）和靶向ROR2的短发夹RNA （sh）可显著抑制骨肉瘤中无序相关形态发生激活因子1 （DAAM1）和RhoA的活性，延缓细胞迁移。ROR1单抗和ROR2 shRNA破坏骨肉瘤细胞的微丝形成。沉默DAAM1（含DAAM1 shRNA）可下调RhoA活性，抑制细胞迁移。野生型DAAM1过表达可挽救DAAM1 shRNA引起的细胞迁移减少。DAAM1和PI3K α /Akt是响应Wnt5a介导骨肉瘤细胞迁移的平行信号通路。由此得出Wnt5a通过ROR1/2受体促进骨肉瘤细胞迁移，进而激活DAAM1和RhoA。
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 PI3K alpha/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.