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Nat Commun. 2016 Feb 4;7:10633. doi: 10.1038/ncomms10633.

PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness.

Author information

1
Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA.
2
Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.
3
Program in Genes and Development, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
4
Graduate School of Biomedical Sciences, University of Texas Health Science Center and MD Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

Cancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated factor (PAF) as a key molecule that controls cancer cell stemness. PAF is highly expressed in breast cancer cells but not in mammary epithelial cells (MECs). In MECs, ectopic expression of PAF induces anchorage-independent cell growth and breast CSC marker expression. In mouse models, conditional PAF expression induces mammary ductal hyperplasia. Moreover, PAF expression endows MECs with a self-renewing capacity and cell heterogeneity generation via Wnt signalling. Conversely, ablation of endogenous PAF induces the loss of breast cancer cell stemness. Further cancer drug repurposing approaches reveal that NVP-AUY922 downregulates PAF and decreases breast cancer cell stemness. Our results unveil an unsuspected role of the PAF-Wnt signalling axis in modulating cell plasticity, which is required for the maintenance of breast cancer cell stemness.

PMID:
26843124
PMCID:
PMC4743006
DOI:
10.1038/ncomms10633
[Indexed for MEDLINE]
Free PMC Article

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