Pennsylvania State University, USA
Yanming Wang is an Associate Professor in Pennsylvania State University, University Park with expertise in Cancer Research, Cell Biology is on ResearchGate. He has 64 publications and 5, 501 citations.
We previously reported that a pan-PAD inhibitor YW3-56 activates p53 target genes to inhibit cancer growth. However, the broad anticancer effi cacy and drug mechanisms of YW3-56 remained largely elusive. Here, gene expression analyses found that ATF4 target genes involved in ER stress response and oxidative stress response were activated by YW3- 56. Depletion of ATF4 greatly attenuated YW3-56 mediated activation of the mTORC1 regulatory genes, SESN2 and DDIT4. Using the ChIP-exo method, high-resolution genomic binding sites of ATF4 and CEBPB were generated prior to and aft er YW3-56 treatment. Moreover, YW3-56 increases cellular ROS levels to facilitate ATF4 target gene activation and cancer cell killing. YW3-56 mediated cell death features mitochondria depletion and autophagy perturbation. At last, YW3-56 treatment eff ectively inhibits the growth of triple negative breast cancer xenograft tumors in nude mice. Taken together, we unveiled the anticancer mechanisms and therapeutic potentials of the pan-PAD inhibitor YW3-56.