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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells
Cancer Cell, Volume 24, No. 2, Year 2013
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Description
Basal-like triple-negative breast cancers (TNBCs) have poor prognosis. To identify basal-like TNBC dependencies, a genome-wide siRNA lethality screen compared two human breast epithelial cell lines transformed with the same genes: basal-like BPLER and myoepithelial HMLER. Expression of the screen's 154 BPLER dependency genes correlated with poor prognosis in breast, but not lung or colon, cancer. Proteasome genes were overrepresented hits. Basal-like TNBC lines were selectively sensitive to proteasome inhibitor drugs relative to normal epithelial, luminal, and mesenchymal TNBC lines. Proteasome inhibition reduced growth of established basal-like TNBC tumors in mice and blocked tumor-initiating cell function and macrometastasis. Proteasome addiction in basal-like TNBCs was mediated by NOXA and linked to MCL-1 dependence. © 2013 Elsevier Inc.
Authors & Co-Authors
Altschuler, Gabriel M.
United States, Boston
Harvard T.h. Chan School of Public Health
Kung, Andrew L.
United States, New York
Columbia University Irving Medical Center
Hide, Winston A.
United States, Boston
Harvard T.h. Chan School of Public Health
Lieberman, Judy
United States, Boston
Boston Children's Hospital
United States, Boston
Harvard Medical School
Statistics
Citations: 127
Authors: 4
Affiliations: 7
Identifiers
Doi:
10.1016/j.ccr.2013.07.008
ISSN:
15356108
Research Areas
Cancer
Substance Abuse