| First Author | Wang X | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10633 | PubMed ID | 26843124 |
| Mgi Jnum | J:236278 | Mgi Id | MGI:5805616 |
| Doi | 10.1038/ncomms10633 | Citation | Wang X, et al. (2016) PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness. Nat Commun 7:10633 |
| abstractText | 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. |
