Molecular mechanisms controlling asymmetric and symmetric self-renewal of cancer stem cells.
Cancer stem cells (CSCs), or alternatively called tumor initiating cells (TICs), are a subpopulation of tumor cells, which possesses the ability to self-renew and differentiate into bulk tumor mass. An accumulating body of evidence suggests that CSCs contribute to the growth and recurrence of tumors and the resistance to chemo- and radiotherapy. CSCs achieve self-renewal through asymmetric division, in which one daughter cell retains the self-renewal ability, and the other is destined to differentiation. Recent studies revealed the mechanisms of asymmetric division in normal stem cells (NSCs) and, to a limited degree, CSCs as well. Asymmetric division initiates when a set of polarity-determining proteins mark the apical side of mother stem cells, which arranges the unequal alignment of mitotic spindle and centrosomes along the apical-basal polarity axis. This subsequently guides the recruitment of fate-determining proteins to the basal side of mother cells. Following cytokinesis, two daughter cells unequally inherit centrosomes, differentiation-promoting fate determinants, and other proteins involved in the maintenance of stemness. Modulation of asymmetric and symmetric division of CSCs may provide new strategies for dual targeting of CSCs and the bulk tumor mass. In this review, we discuss the current understanding of the mechanisms by which NSCs and CSCs achieve asymmetric division, including the functions of polarity- and fate-determining factors.
Protein Metabolism Medical Research Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 110-799 Korea ; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Young Dong
YD
Yoo
Protein Metabolism Medical Research Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 110-799 Korea ; Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul, 110-799 Korea.
Yong Tae
YT
Kwon
Asymmetric and symmetric cell division; Cancer stem cell; Cancer therapy; Fate determinants; Normal tissue stem cells; Self-renewal