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WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP‐14 pathway
Author(s) -
Wang Xingwen,
Zhao Xin,
Yi Zhigang,
Ma Bing,
Wang Hong,
Pu Yanchuan,
Wang Jing,
Wang Shuanke
Publication year - 2018
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10936
Subject(s) - proto oncogene tyrosine protein kinase src , osteosarcoma , wnt5a , wnt signaling pathway , mapk/erk pathway , cancer research , signal transduction , downregulation and upregulation , phosphorylation , microbiology and biotechnology , biology , chemistry , biochemistry , gene
WNT5A, a representative ligand of activating several non‐canonical WNT signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non‐receptor tyrosine kinase SRC is required for WNT5A‐induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC‐mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC‐induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and invasion of human osteosarcoma MG‐63 cells, whereas inhibiting either SRC kinase activity by siRNA‐mediated SRC silence or ERK1/2 phosphorylation by PD98059 treatment suppressed these effects, which suggested that the activation of SRC and ERK1/2 is essential for WNT5A‐induced MG‐63 cells migration and invasion. Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by SRC siRNA. Additionally, our study further demonstrated that MMP‐14 was upregulated after exposure to WNT5A in MG‐63 cells, and the increased expression was blocked by SRC siRNA or PD98059. Collectively, these results indicate that WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP‐14 expression and MG‐63 cells migration and invasion.