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Ref Type Journal Article
PMID (27302160)
Authors Oh AY, Jung YS, Kim J, Lee JH, Cho JH, Chun HY, Park S, Park H, Lim S, Ha NC, Park JS, Park CS, Song GY, Park BJ
Title Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression.
Journal Cancer research
Vol 76
Issue 16
Date 2016 Aug 15
Abstract Text 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.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
SLCB050 SLCB050 is an inhibitor that blocks the AIMP2 splice variant (DX2) from interacting with CDKN2A (p14/ARF), thereby possibly resulting in repression of tumor growth and apoptosis (PMID: 27302160).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown lung small cell carcinoma not applicable Doxorubicin + SLCB050 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of Adriamycin (doxorubicin) plus SLCB050 at low doses in a lung small cell carcinoma cell line xenograft model resulted in decreased tumor volume (PMID: 27302160). 27302160