Document Detail


Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines.
MedLine Citation:
PMID:  21930909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously described four small molecules that reduced the growth of lung adenocarcinoma cell lines with either epidermal growth factor receptor (EGFR) or KRAS mutations in a high-throughout chemical screen. By combining affinity proteomics and gene expression analysis, we now propose superoxide dismutase 1 (SOD1) as the most likely target of one of these small molecules, referred to as lung cancer screen 1 (LCS-1). siRNAs against SOD1 slowed the growth of LCS-1 sensitive cell lines; conversely, expression of a SOD1 cDNA increased proliferation of H358 cells and reduced sensitivity of these cells to LCS-1. In addition, SOD1 enzymatic activity was inhibited in vitro by LCS-1 and two closely related analogs. These results suggest that SOD1 is an LCS-1-binding protein that may act in concert with mutant proteins, such as EGFR and KRAS, to promote cell growth, providing a therapeutic target for compounds like LCS-1.
Authors:
Romel Somwar; Hediye Erdjument-Bromage; Erik Larsson; David Shum; William W Lockwood; Guangli Yang; Chris Sander; Ouathek Ouerfelli; Paul J Tempst; Hakim Djaballah; Harold E Varmus
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-28     Completed Date:  2011-11-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16375-80     Citation Subset:  IM    
Affiliation:
High Throughput Screening Core Facility, and Organic Synthesis Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. somwarr@mskcc.org or harold.varmus@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / enzymology,  pathology*
Cell Division / drug effects*
Cell Line, Tumor
Gene Expression Profiling
Humans
Lung Neoplasms / enzymology,  pathology*
RNA, Small Interfering / genetics
Superoxide Dismutase / drug effects,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
P01 CA129243-03/CA/NCI NIH HHS; P30 CA08748/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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