Epigenetic Regulator Smchd1 Functions as a Tumor Suppressor
- Author(s)
- Leong, HS; Chen, KL; Hu, YF; Lee, S; Corbin, J; Pakusch, M; Murphy, JM; Majewski, IJ; Smyth, GK; Alexander, WS; Hilton, DJ; Blewitt, ME;
- Details
- Publication Year 2013-03-01,Volume 73,Issue #5,Page 1591-1599
- Journal Title
- CANCER RESEARCH
- Publication Type
- Journal Article
- Abstract
- SMCHD1 is an epigenetic modifier of gene expression that is critical to maintain X chromosome inactivation. Here, we show in mouse that genetic inactivation of Smchd1 accelerates tumorigenesis in male mice. Loss of Smchd1 in transformed mouse embryonic fibroblasts increased tumor growth upon transplantation into immunodeficient nude mice. In addition, loss of Smchd1 in E mu-Myc transgenic mice that undergo lymphomagenesis reduced disease latency by 50% relative to control animals. In premalignant Em-Myc transgenic mice deficient in Smchd1, there was an increase in the number of pre-B cells in the periphery, likely accounting for the accelerated disease in these animals. Global gene expression profiling suggested that Smchd1 normally represses genes activated by MLL chimeric fusion proteins in leukemia, implying that Smchd1 loss may work through the same pathways as overexpressed MLL fusion proteins do in leukemia and lymphoma. Notably, we found that SMCHD1 is underexpressed in many types of human hematopoietic malignancy. Together, our observations collectively highlight a hitherto uncharacterized role for SMCHD1 as a candidate tumor suppressor gene in hematopoietic cancers. Cancer Res; 73(5); 1591-9. (C) 2012 AACR.
- Publisher
- AMER ASSOC CANCER RESEARCH
- Keywords
- GROWTH SUPPRESSOR; TRANSGENIC MICE; STEM-CELL; EXPRESSION; GENE; PROTEINS; LEUKEMIA; MOUSE; CHROMOSOME; CARCINOMA
- Research Division(s)
- Cancer And Haematology; Bioinformatics; Structural Biology; Molecular Medicine
- Publisher's Version
- https://doi.org/10.1158/0008-5472.CAN-12-3019
- Terms of Use/Rights Notice
- ©2012 American Association for Cancer Research.
Creation Date: 2013-03-01 12:00:00