High WAVE3 expression correlates with proliferation, migration and invasion in human ovarian cancer
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Jin Lu1,*, Su-Li Wang1,*, Ying-Chun Wang1, Yi-Nan Wu1, Xi Yu2, Wan-Zhou Zhao2 and Jin-Hua Wang1,3
1Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210036, China
2The Nanjing Han & Zaenker Cancer Institute, OG Pharmaceuticals, Nanjing 210036, China
3Jinling Hospital, Nanjing University, Nanjing 210036, China
*These authors have contributed equally to this work
Jin-Hua Wang, email: [email protected]
Keywords: ovarian cancer, WAVE3, cell motility, MMPs
Received: October 29, 2016 Accepted: March 01, 2017 Published: April 17, 2017
Background: 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.
Methods: The 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.
Results: Immunohistochemistry 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.
Conclusions: Our 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.
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