mTOR-dependent transcriptional repression of Pdcd4 tumor suppressor in lung cancer cells

• mTOR as one of the key regulators of Pdcd4 tumor suppressor abundance in lung cancer cells
• A novel mechanism of mTOR-mediated Pdcd4 suppression in cancer cells has been revealed.
• Along with conveying Pdcd4 protein to degradation, mTORC1 inhibits Pdcd4 promoter activity.

Programmed cell death 4 (Pdcd4) tumor suppressor is frequently lost in tumors of various origins including lung cancer, and its loss contributes to tumor progression. However molecular mechanisms underlying Pdcd4 suppression in lung cancer cells remain largely unexplored. Here we investigated molecular mechanisms of Pdcd4 suppression in lung cancer cells. Besides enhanced mTOR-dependent proteasomal degradation of Pdcd4 protein, we found that Pdcd4 transcription is negatively regulated by mTOR signaling, and localized cis-acting element in Pdcd4 promoter responsible for this effect. In conclusion, we described a novel molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR signaling-dependent transcriptional repression of Pdcd4.