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

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  • Xin Wang

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Youn-Sang Jung

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Sohee Jun

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Sunhye Lee

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Wenqi Wang

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Andrea Schneider

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Young Sun Oh

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Steven H. Lin

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Bum-Joon Park

    (Pusan National University)

  • Junjie Chen

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Khandan Keyomarsi

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA)

  • Jae-Il Park

    (University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Z6.6034, Unit 1052, Houston, Texas 77030, USA
    Program in Genes and Development, University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences, University of Texas Health Science Center and MD Anderson Cancer Center)

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.

Suggested Citation

  • 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, 2016. "PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10633
    DOI: 10.1038/ncomms10633
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    Cited by:

    1. Bongjun Kim & Yuanjian Huang & Kyung-Pil Ko & Shengzhe Zhang & Gengyi Zou & Jie Zhang & Moon Jong Kim & Danielle Little & Lisandra Vila Ellis & Margherita Paschini & Sohee Jun & Kwon-Sik Park & Jichao, 2024. "PCLAF-DREAM drives alveolar cell plasticity for lung regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Xiuxiu Lu & Monika Chandravanshi & Venkata R. Sabbasani & Snehal Gaikwad & V. Keith Hughitt & Nana Gyabaah-Kessie & Bradley T. Scroggins & Sudipto Das & Wazo Myint & Michelle E. Clapp & Charles D. Sch, 2024. "A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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