2. Academic Validation
  3. ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells

ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells

  • Mol Cancer Ther. 2015 Apr;14(4):877-88. doi: 10.1158/1535-7163.MCT-14-1093-T.
Shu Wang 1,  Xiangyun Amy Chen 1,  Jing Hu 1,  Jian-Kang Jiang 2,  Yunfei Li 1,  Ka Yim Chan-Salis 1,  Ying Gu 1,  Gong Chen 3,  Craig Thomas 2,  B Franklin Pugh 1,  Yanming Wang 4
Affiliations

Affiliations

  • 1 Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, State College, Pennsylvania.
  • 2 National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.
  • 3 Department of Chemistry, Pennsylvania State University, State College, Pennsylvania.
  • 4 Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, State College, Pennsylvania. yuw12@psu.edu.
PMID: 25612620 DOI: 10.1158/1535-7163.MCT-14-1093-T
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z