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FOXF2 reprograms breast cancer cells into bone metastasis seeds

Author

Listed:
  • Shuo Wang

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Gui-Xi Li

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Cong-Cong Tan

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Rui He

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Li-Juan Kang

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Jun-Tao Lu

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Xiao-Qing Li

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer
    Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Qing-Shan Wang

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer
    Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Pei-Fang Liu

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer
    Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Qiong-Li Zhai

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

  • Yu-Mei Feng

    (Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer
    Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer)

Abstract

Bone metastases occur in most advanced breast cancer patients and cause serious skeletal-related complications. The mechanisms by which bone metastasis seeds develop in primary tumors and specifically colonize the bone remain to be elucidated. Here, we show that forkhead box F2 (FOXF2) functions as a master transcription factor for reprogramming cancer cells into an osteomimetic phenotype by pleiotropic transactivation of the BMP4/SMAD1 signaling pathway and bone-related genes that are expressed at early stages of bone differentiation. The epithelial-to-osteomimicry transition regulated by FOXF2 confers a tendency on cancer cells to metastasize to bone which leads to osteolytic bone lesions. The BMP antagonist Noggin significantly inhibits FOXF2-driven osteolytic bone metastasis of breast cancer cells. Thus, targeting the FOXF2-BMP/SMAD axis might be a promising therapeutic strategy to manage bone metastasis. The role of FOXF2 in transactivating bone-related genes implies a biological function of FOXF2 in regulating bone development and remodeling.

Suggested Citation

  • Shuo Wang & Gui-Xi Li & Cong-Cong Tan & Rui He & Li-Juan Kang & Jun-Tao Lu & Xiao-Qing Li & Qing-Shan Wang & Pei-Fang Liu & Qiong-Li Zhai & Yu-Mei Feng, 2019. "FOXF2 reprograms breast cancer cells into bone metastasis seeds," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10379-7
    DOI: 10.1038/s41467-019-10379-7
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