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Nat Cell Biol. 2014 Jan;16(1):99-107. doi: 10.1038/ncb2889. Epub 2013 Dec 15.

Stem cell quiescence acts as a tumour suppressor in squamous tumours.

Author information

1
1] Department of Molecular Cell and Developmental Biology, UCLA, California 90095, USA [2] Eli and Edythe Broad Center for Regenerative Medicine, UCLA, California 90095, USA.
2
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
3
Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, California 90095, USA.
4
1] Department of Molecular Cell and Developmental Biology, UCLA, California 90095, USA [2] Eli and Edythe Broad Center for Regenerative Medicine, UCLA, California 90095, USA [3] Jonsson Cancer Research Center, UCLA, California 90095, USA [4] Molecular Biology Institute, UCLA, California 90095, USA.

Abstract

In some organs, adult stem cells are uniquely poised to serve as cancer cells of origin. It is unclear, however, whether tumorigenesis is influenced by the activation state of the adult stem cell. Hair follicle stem cells (HFSCs) act as cancer cells of origin for cutaneous squamous cell carcinoma and undergo defined cycles of quiescence and activation. The data presented here show that HFSCs are unable to initiate tumours during the quiescent phase of the hair cycle, indicating that the mechanisms that keep HFSCs dormant are dominant over the gain of oncogenes (such as Ras) or the loss of tumour suppressors (such as p53). Furthermore, Pten activity is necessary for quiescence-based tumour suppression, as its deletion alleviates tumour suppression without affecting proliferation. These data demonstrate that stem cell quiescence is a form of tumour suppression in HFSCs, and that Pten plays a role in maintaining quiescence in the presence of tumorigenic stimuli.

PMID:
24335650
PMCID:
PMC3874399
DOI:
10.1038/ncb2889
[Indexed for MEDLINE]
Free PMC Article

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