2. Academic Validation
  3. Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression

Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression

  • Cancer Res. 2016 Aug 15;76(16):4791-804. doi: 10.1158/0008-5472.CAN-15-1025.
Ah-Young Oh 1,  Youn Sang Jung 1,  Jiseon Kim 2,  Jee-Hyun Lee 2,  Jung-Hyun Cho 1,  Ho-Young Chun 1,  Soyoung Park 1,  Hyunchul Park 3,  Sikeun Lim 3,  Nam-Chul Ha 4,  Jong Sook Park 5,  Choon-Sik Park 5,  Gyu-Yong Song 6,  Bum-Joon Park 7
Affiliations

Affiliations

  • 1 Department of Molecular Biology, Pusan National University, Busan, Republic of Korea (South).
  • 2 College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea (South).
  • 3 Forensic DNA Division, National Forensic Service, Wonju, Republic of Korea (South).
  • 4 Program in Food Science and Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea (South).
  • 5 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi Do, Republic of Korea (South).
  • 6 College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea (South). bjpark1219@pusan.ac.kr gysong@cnu.ac.kr.
  • 7 Department of Molecular Biology, Pusan National University, Busan, Republic of Korea (South). bjpark1219@pusan.ac.kr gysong@cnu.ac.kr.
PMID: 27302160 DOI: 10.1158/0008-5472.CAN-15-1025
Abstract

The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung Cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung Cancer tissues and cells. DX2 prevented oncogene-induced Apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo SLCB050 reduced the viability of human lung Cancer cells, especially small cell lung Cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras-driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non-small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung Cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791-804. ©2016 AACR.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-164536
    DX2-p14/ARF Interaction Inhibitor