Abstract
Wnt5a is classified as a non-transforming Wnt family member and plays complicated roles in oncogenesis and cancer metastasis. However, Wnt5a signaling in osteosarcoma progression remains poorly defined. In this study, we found that Wnt5a stimulated the migration of human osteosarcoma cells (MG-63), with the maximal effect at 100 ng/ml, via enhancing phosphorylation of phosphatidylinositol-3 kinase (PI3K)/Akt. PI3K and Akt showed visible signs of basal phosphorylation and elevated phosphorylation at 15 min after stimulation with Wnt5a. Pharmaceutical inhibition of PI3K with LY294002 significantly blocked the Wnt5a-induced activation of Akt (p-Ser473) and decreased Wnt5a-induced cell migration. Akt siRNA remarkably inhibited Wnt5a-induced cell migration. Additionally, Wnt5a does not alter the total expression and phosphorylation of β-catenin in MG-63 cells. Taken together, we demonstrated for the first time that Wnt5a promoted osteosarcoma cell migration via the PI3K/Akt signaling pathway. These findings could provide a rationale for designing new therapy targeting osteosarcoma metastasis.
Highlights
Osteosarcoma, characterized by a high malignant and metastatic potential, principally affects children and adolescents [1]
Wnt5a stimulates osteosarcoma cell migration in vitro To assess the effect of Wnt5a on osteosarcoma cell migration, we treated MG-63 cells with different doses of recombinant Wnt5a, and measured the migration rate by wound healing assays and Boyden chamber assays
We found that Wnt5a had a potent stimulatory effect on MG-63 cell migration (Figure 1A, 1B)
Summary
Osteosarcoma, characterized by a high malignant and metastatic potential, principally affects children and adolescents [1]. Several improvements in understanding the molecular pathology of metastatic osteosarcoma have been achieved in the last several years [1]. The molecular mechanisms underlying this malignancy are still largely unknown. For this reason, elucidating the signaling pathways involved in the metastatic cascade has become a key goal for developing novel effective therapeutics aimed at reducing osteosarcoma mortality rates. Wnt signaling regulates several developmental and oncogenic processes in both insects and vertebrates [3]. Signals triggered by Wnt are classified into two groups, a canonical β-catenin pathway and non-canonical pathways.
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