The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update

Mutations in the genes of tumor cells and the disorder of immune microenvironment are the main factors of tumor development. The sensitivity of tumor cells to chemotherapy drugs affect the treatment of tumor. Nuclear transcription factor E4BP4 is dysregulated in a variety of malignant tumors. It can suppress the transcription of NFKBIA , RASSF8 , SOSTDC1 , FOXO-induced genes ( TRAIL , FAS , GADD45a and GADD45b ) and Hepcidin , up-regulate RCAN1-1 and PRNP , activate mTOR and p38 in cancer cells. Also, E4BP4 can regulate tumor immune microenvironment. TGFb1/Smad3/E4BP4/ IFNγ axis in NK cells plays an important role in antitumor immunotherapy. Over expression of E4BP4 inhibited the development of Th17 cells by directly binding to the RORγt promoter. Moreover, recent studies have shown that E4BP4 inhibited the expression of multidrug resistance genes. In this review, we summarize the molecular mechanism of E4BP4 in cancer cellular process, the effects of E4BP4 in cancer immunotherapy and antitumor drug resistance, to provide theoretical basis for tumor treatment strategies targeting E4BP4.