Upsides and downsides to polarity and asymmetric cell division in leukemia.
The notion that polarity regulators can act as tumor suppressors in epithelial cells is now well accepted. The function of these proteins in lymphocytes is less well explored, and their possible function as suppressors of leukemia has had little attention so far. We review the literature on lymphocyte polarity and the growing recognition that polarity proteins have an important function in lymphocyte function. We then describe molecular relationships between the polarity network and signaling pathways that have been implicated in leukemogenesis, which suggest mechanisms by which the polarity network might impact on leukemogenesis. We particularly focus on the possibility that disruption of polarity might alter asymmetric cell division (ACD), and that this might be a leukemia-initiating event. We also explore the converse possibility that leukemic stem cells might be produced or maintained by ACD, and therefore that Dlg, Scribble and Lgl might be important regulators of this process.
Hawkins
E D
ED
Immune Signalling Laboratory, Cancer Immunology, Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Russell
S M
SM
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic; D053263:Gene Regulatory Networks / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics