Fibulin-3 knockdown inhibits cervical cancer cell growth and metastasis in vitro and in vivo.

To explore the function of fibulin-3 in cervical carcinoma malignant cell growth and metastasis, fibulin-3 expression in normal cervical tissue, cervical intraepithelial neoplasia (CIN), and cervical carcinoma were evaluated by immunohistochemistry. Quantitative real-time-polymerase chain reaction, western blotting, and immunocytochemistry were performed to assess the expression of fibulin-3 at mRNA and protein levels in different invasive clone sublines. Fibulin-3 shRNA and fibulin-3 cDNA were used to transfect the strongly and weakly invasive clone sublines. Using in vitro and in vivo functional assays, we investigated the effects of down-regulating and up-regulating fibulin-3 expression on the proliferation and invasion of different clone sublines. Epithelial mesenchymal transition (EMT) and its signaling pathways PI3K/AKT and ERK were studied carefully in lentiviral transfection systems. Fibulin-3 was upregulated in cervical carcinoma, and its overexpression was significantly related with malignant phenotype and poor prognosis of cervical carcinoma. Fibulin-3 promoted cervical cancer cell invasive capabilities by eliciting EMT and activating the PI3K-Akt-mTOR signal transduction pathway. Fibulin-3 could facilitate the process of cervical cancer development. The results presented here will help develop novel prognostic factors and possible therapeutic options for patients with cervical cancer.