The PI3K/Akt/mTOR signaling pathway mediates insulin-like growth factor 1-induced E-cadherin down-regulation and cell proliferation in ovarian cancer cells

Insulin-like growth factor 1 (IGF1) is produced by ovarian cancer cells and it has been suggested that it plays an important role in tumor progression. In this study, we report that IGF1 treatment down-regulated E-cadherin by up-regulating E-cadherin transcriptional repressors, Snail and Slug, in human ovarian cancer cells. The pharmacological inhibition of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) suggests that PI3K/Akt/mTOR signaling is required for IGF1-induced E-cadherin down-regulation. Moreover, IGF1 up-regulated Snail and Slug expression via the PI3K/Akt/mTOR signaling pathway. Finally, IGF1-induced cell proliferation was abolished by inhibiting PI3K/Akt/mTOR signaling. This study demonstrates a novel mechanism in which IGF1 down-regulates E-cadherin expression through the activation of PI3K/Akt/mTOR signaling and the up-regulation of Snail and Slug in human ovarian cancer cells.

► IGF1 decreases E-cadherin expression via the PI3K/Akt/mTOR signaling pathway in ovarian cancer cells. ► IGF1 increases Snail and Slug expression via the PI3K/Akt/mTOR signaling pathway. ► Inhibition of the PI3K/Akt/mTOR signaling pathway abolishes the IGF1-induced cell proliferation in ovarian cancer cells.