Sonic hedgehog-Gli1 signals promote epithelial-mesenchymal transition in ovarian cancer by mediating PI3K/AKT pathway

摘要

Epithelial-mesenchymal transition (EMT) has been reported to play an important role in distant metastasis in cancer-related disease. A large number of studies have shown that sonic hedgehog-glioma-associated oncogene 1 (Shh-Gli1) signals participate in the process of EMT; however, the role and mechanism of Shh-Gli1 signals in the progression of EMT in ovarian cancer remain largely unknown. First, we investigated the occurrence of EMT and invasion and migration ability in ovarian cancer cells stimulated by different concentration of Shh-Gli1 signals agonist purmorphamine in vitro. Then, Akt siRNA was transfected into ovarian cancer cells which already stimulated by purmorphamine to elucidate the molecular mechanism underlying the pathogenesis of EMT in ovarian cancer. Gli1 expression was significantly enhanced in ovarian cancer cells after stimulated by purmorphamine. In addition, Gli1 up-regulation promoted EMT, invasion and migration ability of ovarian cancer cells. Furthermore, we validated a cross talk between Shh-Gli1 signals and PI3K-Akt pathway in the occurrence of EMT in ovarian cancer cells. These findings revealed a novel role for Shh-Gli1 signals in EMT in ovarian cancer and provided for us a potential therapeutic target for the suppression of EMT, invasion and metastasis in ovarian cancer.