Correlation Engine 2.0
Clear Search sequence regions


  • behaviour (1)
  • breast cancer (4)
  • breast neoplasms (1)
  • c src (2)
  • female (1)
  • fibrils (2)
  • fibronectin (2)
  • humans (1)
  • integrin (1)
  • lung (3)
  • metastasis (2)
  • mice (1)
  • mice nude (1)
  • proteins pp60( c- src) (4)
  • regulates (1)
  • rna (1)
  • Sfrp2 (4)
  • signal (4)
  • tumour (2)
  • Sizes of these terms reflect their relevance to your search.

    The process of metastasis is complex1. In breast cancer, there are frequently long time intervals between cells leaving the primary tumour and growth of overt metastases2,3. Reasons for disease indolence and subsequent transition back to aggressive growth include interactions with myeloid and fibroblastic cells in the tumour microenvironment and ongoing immune surveillance4-6. However, the signals that cause actively growing cells to enter an indolent state, thereby enabling them to survive for extended periods of time, are not well understood. Here we reveal how the behaviour of indolent breast cancer cells in the lung is determined by their interactions with alveolar epithelial cells, in particular alveolar type 1 cells. This promotes the formation of fibronectin fibrils by indolent cells that drive integrin-dependent pro-survival signals. Combined in vivo RNA sequencing and drop-out screening identified secreted frizzled-related protein 2 (SFRP2) as a key mediator of this interaction. Sfrp2 is induced in breast cancer cells by signals from lung epithelial cells and promotes fibronectin fibril formation and survival, whereas blockade of Sfrp2 expression reduces the burden of indolent disease.

    Citation

    Marco Montagner, Rahul Bhome, Steven Hooper, Probir Chakravarty, Xiao Qin, Jahangir Sufi, Ajay Bhargava, Colin D H Ratcliffe, Yutaka Naito, Arianna Pocaterra, Christopher J Tape, Erik Sahai. Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination. Nature cell biology. 2020 Mar;22(3):289-296

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 32094692

    View Full Text