TY - JOUR
T1 - SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer
AU - Li, Lianjie
AU - Shen, Chuan
AU - Nakamura, Eijiro
AU - Ando, Kiyohiro
AU - Signoretti, Sabina
AU - Beroukhim, Rameen
AU - Cowley, Glenn S.
AU - Lizotte, Patrick
AU - Liberzon, Ella
AU - Bair, Steven
AU - Root, David E.
AU - Tamayo, Pablo
AU - Tsherniak, Aviad
AU - Cheng, Su Chun
AU - Tabak, Barbara
AU - Jacobsen, Anders
AU - Hakimi, A. Ari
AU - Schultz, Nikolaus
AU - Ciriello, Giovanni
AU - Sander, Chris
AU - Hsieh, James J.
AU - Kaelin, William G.
N1 - Funding Information:
We thank members of the W.G.K. laboratory for useful comments and Drs. Eileen White and David M. Sabatini for reagents. W.G.K. is a Howard Hughes Medical Institute investigator and supported by grants from the National Institutes of Health.
PY - 2013/12/9
Y1 - 2013/12/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84891957021&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2013.10.025
DO - 10.1016/j.ccr.2013.10.025
M3 - Article
C2 - 24332042
AN - SCOPUS:84891957021
SN - 1535-6108
VL - 24
SP - 738
EP - 750
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -