title: It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.
abstract: During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion.
authors.affiliation: Program in Cellular and Molecular Biology, USA.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Janssens
authors.affiliation: Program in Cellular and Molecular Biology, USA; Center for Stem Cell Biology, Life Sciences Institute, USA; Division of Molecular Medicine and Genetics, Department of Internal Medicine, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: leecheng@umich.edu.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D004330:Drosophila; D006801:Humans; D007814:Larva; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*
keywords: Brain tumor; Cancer stem cell; Cell of origin; Earmuff; Intermediate progenitor; Neuroblast; Numb; SWI/SNF