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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2013
Journal
Cancer Cell
Volume
24
Issue
6
Pages
738-50
Date Published
2013 Dec 09
ISSN
1878-3686
URL
DOI
10.1016/j.ccr.2013.10.025
PubMed ID
24332042
PubMed Central ID
PMC3910168
Links
Grant list
R01 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