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Cancer Cell DOI:10.1016/j.ccr.2013.10.025

SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer.

Publication TypeJournal Article
Year of Publication2013
AuthorsLi, L, Shen, C, Nakamura, E, Ando, K, Signoretti, S, Beroukhim, R, Cowley, GS, Lizotte, P, Liberzon, E, Bair, S, Root, DE, Tamayo, P, Tsherniak, A, Cheng, S-C, Tabak, B, Jacobsen, A, A Hakimi, A, Schultz, N, Ciriello, G, Sander, C, Hsieh, JJ, Kaelin, WG
JournalCancer Cell
Volume24
Issue6
Pages738-50
Date Published2013 Dec 09
ISSN1878-3686
KeywordsAdaptor Proteins, Signal Transducing, Animals, Base Sequence, Carcinoma, Renal Cell, Cell Line, Tumor, Chromosomes, Human, Pair 5, Gene Dosage, Humans, Kidney Neoplasms, Mice, Molecular Sequence Data, NF-E2-Related Factor 2, Sequestosome-1 Protein
Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and is often linked to loss of chromosome 3p, which harbors the VHL tumor suppressor gene, loss of chromosome 14q, which includes HIF1A, and gain of chromosome 5q. The relevant target(s) on chromosome 5q is not known. Here, we show that 5q amplification leads to overexpression of the SQSTM1 oncogene in ccRCC lines and tumors. Overexpression of SQSTM1 in ccRCC lines promoted resistance to redox stress and increased soft agar growth, while downregulation of SQSTM1 decreased resistance to redox stress, impaired cellular fitness, and decreased tumor formation. Therefore, the selection pressure to amplify 5q in ccRCC is driven, at least partly, by SQSTM1.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1535-6108(13)00492-3
DOI10.1016/j.ccr.2013.10.025
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24332042?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID24332042
PubMed Central IDPMC3910168
Grant ListR01 CA068490 / CA / NCI NIH HHS / United States
P50 CA101942 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
T32 CA082088 / CA / NCI NIH HHS / United States
R01 CA121941 / CA / NCI NIH HHS / United States