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Inactivation of SMC2 shows a synergistic lethal response inMYCN-amplified neuroblastoma cells

Year: 2014
Type: article
Abstract: The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis. This study demonstrates that the gene encoding the condensin complex subunit SMC2 is transcriptionally regulated by MYCN. SMC2 also transcriptionally regulates DNA damage response genes in cooperation with MYCN. Downregulation of SMC2 induced DNA damage and showed a synergistic lethal response in MYCN-amplified/overexpression cells, leading to apoptosis in human neuroblastoma cells. Finally, this study found that patients bearing MYCN-amplified tumors showed improved survival when SMC2 expression was low. These results identify novel functions of SMC2 in DNA damage response, and we propose that SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma.
Source: Cell Cycle
DOI: 10.4161/cc.27983
Authors: Yuko Murakami-Tonami, Satoshi Kishida, Ichiro Takeuchi, Yuki Katou, John M Maris, Hitoshi Ichikawa, Yutaka Kondo, Yoshitaka Sekido, Katsuhiko Shirahige, Hiroshi Murakami, Kenji Kadomatsu
Institutions: Nagoya University, Nagoya Institute of Technology, The University of Tokyo, Children's Hospital of Philadelphia, University of Pennsylvania, National Cancer Centre Japan, National Cancer Institute, Aichi Cancer Center, Aichi Cancer Center Research Institute, Department of Biological Sciences, Chuo University
Language: English
Field: Medicine
Open Access status: hybrid
OpenAlex ID: W2041539092
FWCI: 2.651
Cites: 59
Cited by: 36
Related to: 10