title: Stem cell quiescence acts as a tumour suppressor in squamous tumours.
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.
authors: 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.
authors: A C
authors: AC
authors: White
authors: 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.
authors: J K
authors: JK
authors: Khuu
authors: 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.
authors: C Y
authors: CY
authors: Dang
authors: 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.
authors: J
authors: J
authors: Hu
authors: 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.
authors: K V
authors: KV
authors: Tran
authors: 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.
authors: A
authors: A
authors: Liu
authors: 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.
authors: S
authors: S
authors: Gomez
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors: Z
authors: Z
authors: Zhang
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors: R
authors: R
authors: Yi
authors: Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, California 90095, USA.
authors: P
authors: P
authors: Scumpia
authors: 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.
authors: M
authors: M
authors: Grigorian
authors: 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.
authors: W E
authors: WE
authors: Lowry
mesh_terms: D000328:Adult; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D005434:Flow Cytometry; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018859:Hair Follicle / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D019426:Integrases / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D050505:Mutant Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins