Abstract:
:We previously reported that a pan-PAD inhibitor, YW3-56, activates p53 target genes to inhibit cancer growth. However, the p53-independent anticancer activity and molecular mechanisms of YW3-56 remain largely elusive. Here, gene expression analyses found that ATF4 target genes involved in endoplasmic reticulum (ER) 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 responsive to YW3-56 treatment were generated. In human breast cancer cells, YW3-56-mediated cell death features mitochondria depletion and autophagy perturbation. Moreover, YW3-56 treatment effectively 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.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Wang S,Chen XA,Hu J,Jiang JK,Li Y,Chan-Salis KY,Gu Y,Chen G,Thomas C,Pugh BF,Wang Ydoi
10.1158/1535-7163.MCT-14-1093-Tsubject
Has Abstractpub_date
2015-04-01 00:00:00pages
877-88issue
4eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-14-1093-Tjournal_volume
14pub_type
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