Abstract
BackgroundWiskott-Aldrich syndrome verprolin-homologous (WAVE) 3, a member of the WASP/WAVE family of proteins, plays a critical role in cell motility and acts as an oncogene in some human cancers, but no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression.MethodsThe expression of WAVE3 in human ovarian cancer and normal tissue was analyzed by immunohistochemistry. WAVE3 gene and protein expression in different human ovarian cancer cell lines was tested by RT-PCR and western blotting. Stable cells of WAVE3-knockdown in SKOV3 cells or transfected high expression in A2780 cells were constructed. The WAVE3 expression and its correlation with MMPs, p38 MAPK and other factors were studied. The relationship between WAVE3 and oncogenicity in vivo was also evaluated by nude mice xenograft model.ResultsImmunohistochemistry staining showed the highest WAVE3 expression in ovarian cancer metastases, high in ovarian cancer and weak in normal. In different cell lines, SKOV3 cells showed the highest WAVE3 expression, A2780 cells expressed the lowest. Elevated WAVE3 expression in A2780 cells promoted proliferation and decreased apoptosis, increased the cell number in G2/M phase and promoted migration significantly. Correspondingly, knockdown of WAVE3 in SKOV3 cells showed opposite effects. The WAVE3 expression showed positive correlation with MMPs, NF-κB, COX-2, VEGF and phospho-p38 MAPK, but not p38. The high expression of WAVE3 promoted tumorigenesis in vivo.ConclusionsOur results suggested that WAVE3 may be pivotal in ovarian cancer cell motility, invasion and oncogenesis, which might be related with MMPs production and p38 MAPK pathway.
Highlights
Ovaries are located in the depth of the pelvic
Our results suggested that WAVE3 may be pivotal in ovarian cancer cell motility, invasion and oncogenesis, which might be related with Matrix metalloproteinases (MMPs) production and p38 MAPK pathway
Though WAVE3 have been proved that might act as an oncogene in some human cancers [12, 14,15,16,17], but to the best of our knowledge, there is no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression
Summary
Ovaries are located in the depth of the pelvic. Ovarian cancer is one of the most common gynecological malignancies with high mortality rate of the patients due to its easy invasion and metastasis [1]. Ovarian cancer invasion and metastasis are known as a complex and multi-step cell progresses and associated with many interacting proteins expression, and cellular migration plays a critical role for the ability of tumor cells to metastasize locally and to distant sites [3]. Though WAVE3 have been proved that might act as an oncogene in some human cancers [12, 14,15,16,17], but to the best of our knowledge, there is no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression. Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3, a member of the WASP/WAVE family of proteins, plays a critical role in cell motility and acts as an oncogene in some human cancers, but no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression
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