Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 39, Pages 16375-16380Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1113554108
Keywords
chemical biology; target discovery and validation; gene interaction network
Categories
Funding
- National Institutes of Health [PO1 CA129243-03]
- National Cancer Institute Cancer Center [P30 CA08748]
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center of MSKCC
- William Randolph Hearst Fund in Experimental Therapeutics
- Lillian S. Wells Foundation
- Swedish Research Council
- Canadian Institutes of Health Research
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available