Genes that affect both cell growth and polarity mediate stem cell quiescence.
Stem cells possess the capacity to expand and self-renew and do so by dividing in either a symmetrical or an asymmetrical manner. Under particular circumstances, some stem cell populations can undergo prolonged cell cycle arrest or quiescence, until they are triggered to divide by a given stimulus. In cancer treatment, these populations represent a significant roadblock to efficient therapies as their non-dividing state renders them refractory to most commonly used cytotoxic interventions. In certain organisms, germline stem cells undergo quiescence if animals experience inappropriate growth conditions, and recent studies have determined that the level of insulin signaling is key in the regulation of their proliferation rate, and that it functions through at least two tumor suppressor genes, PTEN and LKB1. These gene products regulate both growth and polarity in diverse cellular contexts, while it remains unclear how they can modulate cell division and prevent tumorigenesis through each of these functions, and whether indeed these functions are separable. We hope that understanding how these tumor suppressor genes impinge on quiescent stem cell populations could provide us with a means of designing more effective therapies to reduce the frequency of stem cell-derived tumor growth that occurs following treatment.
Narbonne
Patrick
P
Department of Biology, McGill University, Montreal, Quebec, Canada.
Roy
Richard
R
D000818:Animals; D002455:Cell Division; D016764:Cell Polarity; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase