Stem cell quiescence acts as a tumour suppressor in squamous tumours

A C White; J K Khuu; C Y Dang; J Hu; K V Tran; A Liu; S Gomez; Z Zhang; R Yi; P Scumpia; M Grigorian; W E Lowry

doi:10.1038/ncb2889

Stem cell quiescence acts as a tumour suppressor in squamous tumours

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

Authors

A C White¹, J K Khuu¹, C Y Dang¹, J Hu¹, K V Tran¹, A Liu¹, S Gomez¹, Z Zhang², R Yi², P Scumpia³, M Grigorian¹, W E Lowry⁴

Affiliations

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.

PMID: 24335650
PMCID: PMC3874399
DOI: 10.1038/ncb2889

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / pathology*
Cell Cycle* / genetics
Cell Proliferation
Disease Progression
Flow Cytometry
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hair Follicle / pathology
Humans
Hyperplasia
Integrases / metabolism
Mice
Mutant Proteins / metabolism
PTEN Phosphohydrolase / deficiency
PTEN Phosphohydrolase / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins p21(ras) / metabolism
Signal Transduction / genetics
Skin Neoplasms / genetics
Skin Neoplasms / pathology*
Stem Cells / pathology*
Transcription Factors / metabolism
Tumor Suppressor Protein p53 / metabolism
ras Proteins / metabolism

Substances

KRAS protein, human
Mutant Proteins
Proto-Oncogene Proteins
Transcription Factors
Tumor Suppressor Protein p53
Cre recombinase
Integrases
PTEN Phosphohydrolase
Hras protein, mouse
Proto-Oncogene Proteins p21(ras)
ras Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding