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Linking the SWI/SNF complex to prostate cancer

Nature Genetics volume 45, pages 1268–1269 (2013)Cite this article

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Genes encoding subunits of the SWI/SNF chromatin-remodeling complex constitute, collectively, one of the most frequently mutated targets in cancer. Although mutations in SWI/SNF genes are uncommon in prostate cancer, a new study shows that SChLAP1, a long noncoding RNA frequently expressed in aggressive prostate tumors, drives cancer by directly disrupting SNF5, a core subunit of the SWI/SNF complex.

Despite improvements in screening and early detection, prostate cancer remains the second leading cause of cancer mortality in men1. However, individual cases of prostate cancer can display markedly different clinical behavior, ranging from indolent to highly aggressive, metastatic cancers. Thus, ongoing efforts are aimed at identifying biomarkers of aggressive disease and investigating underlying mechanisms. For example, one subset of more aggressive prostate tumors is characterized by the overexpression of EZH2, a member of the PRC2 epigenetic regulatory complex2. Recently, the examination of causal links has expanded to include long noncoding RNAs (lncRNAs) aberrantly expressed in cancer, although the mechanisms by which these lncRNAs drive oncogenesis are just beginning to be understood3,4. In prostate cancer alone, multiple lncRNAs have been described as being abnormally expressed at high levels in cancer cells, with nearly a quarter of transcripts found to be lncRNAs or to be derived from otherwise unannotated sequences4,5,6. On page 1392 of this issue, Arul Chinnaiyan and colleagues7 focus on one of these lncRNAs, called SChLAP1, and identify a mechanism by which it contributes to prostate cancer growth.

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Figure 1: Aberrantly high expression of SChLAP1 in aggressive prostate cancers inhibits SWI/SNF-mediated epigenetic regulation.

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Authors and Affiliations

  1. Department of Pediatric Oncology, the Division of Hematology-Oncology, Boston Children's Hospital and the Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

    Ryan S Lee & Charles W M Roberts

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  1. Ryan S Lee
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  2. Charles W M Roberts
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Correspondence to Charles W M Roberts.

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Lee, R., Roberts, C. Linking the SWI/SNF complex to prostate cancer. Nat Genet 45, 1268–1269 (2013). https://doi.org/10.1038/ng.2805

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