PAF-Wnt Signaling-induced Cell Plasticity is Required for Maintenance of Breast Cancer Cell Stemness

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Feb 5

PMID 26843124

Citations 42

Authors

Xin Wang

Youn-Sang Jung

Sohee Jun

Sunhye Lee

Wenqi Wang

Andrea Schneider

Young Sun Oh

Steven H Lin

Bum-Joon Park

Junjie Chen

Khandan Keyomarsi

Jae-Il Park

Affiliations

Soon will be listed here.

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.

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