Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin

Charlene S.L. Hoi, Song Eun Lee, Shu Yang Lu, David J. McDermitt, Karen M. Osorio, Caroline M. Piskun, Rachel M. Peters, Ralf Paus, Tudorita Tumbar

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Runx1/AML1 is a transcription factor implicated in tissue stem cell regulation and belongs to the small Runx family of cancer genes. In the hair follicle (HF), Runx1 epithelial deletion in morphogenesis impairs normal adult hair homeostasis (cycle) and blocks adult hair follicle stem cells (HFSCs) in quiescence. Here, we show that these effects are overcome later in adulthood. By deleting Runx1 after the end of morphogenesis, we demonstrate its direct role in promoting anagen onset and HFSC proliferation. Runx1 deletion resulted in cyclin-dependent kinase inhibitor Cdkn1a (p21) upregulation. Interfering with Runx1 function in cultured HFSCs impaired their proliferation and normal G 0/G1 and G1/S cell cycle progression. The proliferation defect could be rescued by Runx1 readdition or by p21 deletion. Chemically induced skin tumorigenesis in mice turned on broad Runx1 expression in regions of the skin epithelium, papillomas, and squamous cell carcinomas. In addition, it revealed reduced rates of tumor formation in the absence of Runx1 that were accompanied by decreased epithelial levels of phospho-Stat3. Runx1 protein expression was similar in normal human and mouse hair cycles. We propose that Runx1 may act as a skin oncogene by directly promoting proliferation of the epithelial cells.

Original languageEnglish (US)
Pages (from-to)2518-2536
Number of pages19
JournalMolecular and cellular biology
Volume30
Issue number10
DOIs
StatePublished - May 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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