SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer

Lianjie Li, Chuan Shen, Eijiro Nakamura, Kiyohiro Ando, Sabina Signoretti, Rameen Beroukhim, Glenn S. Cowley, Patrick Lizotte, Ella Liberzon, Steven Bair, David E. Root, Pablo Tamayo, Aviad Tsherniak, Su Chun Cheng, Barbara Tabak, Anders Jacobsen, A. Ari Hakimi, Nikolaus Schultz, Giovanni Ciriello, Chris SanderJames J. Hsieh, William G. Kaelin

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish
Pages (from-to)738-750
Number of pages13
JournalCancer Cell
Volume24
Issue number6
DOIs
StatePublished - Dec 9 2013

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