WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer.

Abstract

Alterations in Wiskott-Aldrich syndrome protein family verprolin-homologous protein 3 (WAVE3) expression play various roles in certain types of cancer. However, the roles of WAVE3 expression in pancreatic cancer remain unknown. The present retrospective study demonstrated that WAVE3 expression was higher in cancerous pancreatic tissues than in non-neoplastic tissues. Moreover, WAVE3 overexpression was related to lymphatic metastasis, a poor differentiation and high pre-operative CA19-9 levels and was an adverse prognostic factor for patients with pancreatic cancer. In vitro, the knockdown of WAVE3 inhibited the proliferative, migratory and invasive potential of pancreatic cancer cells and promoted cell apoptosis. Western blot analysis demonstrated that WAVE3 influenced the protein kinase B (PBK/AKT) pathway by suppressing the expression of pyruvate dehydrogenase kinase isoform 2 (PDK2) and then negatively inhibiting the phosphorylation of Ser473 on AKT. Furthermore, the expression of AKT pathway downstream proteins [certain epithelial-mesenchymal transition (EMT)-related proteins, p53, Bcl-2 and cyclin D1] was accordingly altered. Taken together, our findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway, and targeting WAVE3 and/or the AKT pathway may potentially serve as a treatment strategy for pancreatic cancer.

• Authors: Shaobin Huang, Chensong Huang, Wei Chen, Yifeng Liu, Xiaoyu Yin, Jiaming Lai, Lijian Liang, Qian Wang, Anxun Wang, Chaoxu Zheng
• Journal: International journal of oncology (Int J Oncol) Vol. 53 Issue 2 Pg. 672-684 (Aug 2018) ISSN: 1791-2423 [Electronic] Greece
• PMID: 29845225 (Publication Type: Journal Article)

Chemical References

• WASF3 protein, human
• Wiskott-Aldrich Syndrome Protein Family
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• Neoplasm Grading
• Neoplasm Invasiveness
• Pancreatic Neoplasms (genetics, metabolism, pathology)
• Phosphorylation
• Prognosis
• Proto-Oncogene Proteins c-akt (metabolism)
• Retrospective Studies
• Up-Regulation
• Wiskott-Aldrich Syndrome Protein Family (genetics, metabolism)