Most cancer-initiating cells (CICs) are quiescent and therefore resistant to anticancer drugs that preferentially target dividing cells. CICs that survive therapy are a potential cause of relapse. Elucidation of the mechanism by which CICs maintain quiescence is thus critical for the elimination of cancer. Here we show that Fbxw7 plays a pivotal role in maintenance of quiescence in leukemia-initiating cells (LICs) of chronic myeloid leukemia. Our findings reveal that ablation of Fbxw7 in LICs results in deregulated activation of c-Myc and impaired maintenance of quiescence followed by p53-dependent apoptosis and consequent cell exhaustion. Moreover, they provide a rationale for Fbxw7-targeted therapy to sensitize LICs to currently available drugs by interrupting their quiescence, potentially resulting in a substantial survival benefit.
Researcher Information
JST CREST Research Area “The Dynamic Mechanism of and Fundamental Technology for Biological System”,
Research Theme : “Establishment of the analytical basis toward comprehensive understanding of the ubiquitin system”
Journal Information
Shoichiro Takeishi, Akinobu Matsumoto, Ichiro Onoyama, Kazuhito Naka, Atsushi Hirao, Keiichi I. Nakayama
“Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence”
Cancer Cell, 2013
doi: 10.1016/j.ccr.2013.01.026
Contact
[About Research]
Professor, Medical Institute of Bioregulation, Kyushu University
Keiichi Nakayama
E-mail:
HP: http://www.bioreg.kyushu-u.ac.jp/saibou/index_en.html
[About Program]
Life Innovation Group
Department of Innovation Research
Japan Science and Technology Agency
Shigeru Ishimasa
E-mail:
HP: http://www.jst.go.jp/kisoken/crest/en/index.html