MassIVE MSV000092332

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NDUFA12 as a functional target of the anticancer compound Ertredin in human hepatoma cells revealed by label-free chemical proteomics

Description

Many studies have been attempted to develop new agents that target EGFR mutants or regulate downstream players in various cancers. A new small molecule, Ertredin, was discovered through cell-based screening to inhibit EGFRvIII mutant cancer cells. Previous studies have shown that Ertredin effectively inhibits anchorage-independent 3D growth of sphere-forming cells transfected with EGFRvIII mutant cDNA. However, the underlying mechanism remains to be elucidated. In this study, we investigated the target protein of Ertredin by combining DARTS with LC-MS/MS using label-free Ertredin as a bait and HepG2 cell lysates as a proteome pool. As a result, NADH dehydrogenase 1 alpha subcomplex subunit 12, NDUFA12, was identified as one of the binding proteins of Ertredin responsible for the biological activity of the compound. The interaction between NDUFA12 and Ertredin was validated by DARTS and CETSA methods. In addition, genetic knockdown of the identified target NDUFA12 was validated with respect to its association with cell proliferation. Taken together, NDUFA12 is identified as a biologically relevant target protein of Ertredin to address an anti-tumor activity of the compound and these results provide insights into a role of NDUFA12 as a downstream player of EGFRvIII mutant. [doi:10.25345/C52J68F5G] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Ertredin ; Anti-cancer agent ; Target Identification ; DARTS ; LC-MS/MS ; CETSA ; Mitochondria complex 1 ; NDUFA12

Contact

Principal Investigators:
(in alphabetical order)
Ho Jeong Kwon, College of Life Science and Biotechnology, Yonsei University, South Korea
Submitting User: juyeon4444
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