Role of Fbxw7 in the maintenance of normal stem cells and cancer-initiating cells.
In addition to the properties of self-renewal and multipotency, stem cells are characterised by their distinct cell cycle status. Somatic stem cells are maintained in a quiescent state but switch reversibly from quiescence to proliferation as needed. On the other hand, embryonic stem cells and induced pluripotent stem cells proliferate rapidly until the induction of differentiation results in inhibition of cell cycle progression. Uncovering the mechanisms underlying cell cycle control in stem cells should thus provide insight into regulation of the balance between self-renewal and differentiation, a key goal of stem cell biology. Recent research has shown that cancer-initiating cells (CICs), a cell population with stem cell-like properties in cancer, are also quiescent, with this characteristic conferring resistance to anticancer therapies that target dividing cells. Elucidation of the mechanisms of CIC quiescence might therefore be expected to provide a basis for the eradication of cancer. This review summarises our current understanding of the role of F-box and WD40 repeat domain-containing 7 (Fbxw7), a key regulator of the cell cycle, in the maintenance of normal stem cells and CICs, as well as attempts to define future challenges in this field.
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
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Takeishi
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
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Nakayama
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases