Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition, as well as the migration and invasion of cervical cancer.

Abstract

Brain-derived neurotrophic factor(BDNF) has previously been demonstrated to be associated with several types of cancer. In addition, its receptor, tropomyosin related kinaseB(TrkB) is involved in tumor invasion and metastasis. Epithelial-mesenchymal transition(EMT) is associated with metastasis in cancers. Thus, The aim of the present study was to examine whether BDNF/TrKB expression is linked to a poor survival and the acquisition of the EMT phenotype in cervical cancer. We found that a high positive expression of BDNF/TrKB was associated with poor survival in cervical cancer. Our results revealed that high expression levels of BDNF/TrKB were observed in cervical cancer compared to normal cells. Importantly, we demonstrated that the silencing of TrKB suppressed the activation of EMT via the downregulation of N-cadherin, vimentin, matrix metalloproteinase(MMP)2 and MMP9, and the upregulation of E-cadherin and tissue inhibitor of metalloproteinases(TIMP)2, which resulted in suppressed cell proliferation, migration and invasion. Furthermore, high phosphorylation levels of ERK and Akt were observed in the cervical cancer cells, while these levels were decreased in the cells in which TrKB was knocked down. On the whole, these findings suggest that the BDNF/TrKB pathway is a promising target for the prevention of tumor proliferation, invasion, metastasis and EMT in cervical cancer cells.