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@ARTICLE{Wutschka:169894,
      author       = {J. Wutschka$^*$ and B. Kast$^*$ and M. Sator-Schmitt$^*$
                      and S. Appak-Baskoy$^*$ and J. Hess$^*$ and H.-P. Sinn and
                      P. Angel$^*$ and M. Schorpp-Kistner$^*$},
      title        = {{JUNB} suppresses distant metastasis by influencing the
                      initial metastatic stage.},
      journal      = {Clinical $\&$ experimental metastasis},
      volume       = {38},
      number       = {4},
      issn         = {1573-7276},
      address      = {Dordrecht},
      publisher    = {Springer Science + Business Media B.V.},
      reportid     = {DKFZ-2021-01628},
      pages        = {411-423},
      year         = {2021},
      note         = {DKFZ-ZMBH Alliance / #EA:A100#LA:A100#/ 2021
                      Aug;38(4):411-423},
      abstract     = {The complex interactions between cells of the tumor
                      microenvironment and cancer cells are considered a major
                      determinant of cancer progression and metastasis. Yet, our
                      understanding of the mechanisms of metastatic disease is not
                      sufficient to successfully treat patients with
                      advanced-stage cancer. JUNB is a member of the AP-1
                      transcription factor family shown to be frequently
                      deregulated in human cancer and associated with invasion and
                      metastasis. A strikingly high stromal JUNB expression in
                      human breast cancer samples prompted us to functionally
                      investigate the consequences of JUNB loss in cells of the
                      tumor microenvironment on cancer progression and metastasis
                      in mice. To adequately mimic the clinical situation, we
                      applied a syngeneic spontaneous breast cancer metastasis
                      model followed by primary tumor resection and identified
                      stromal JUNB as a potent suppressor of distant metastasis.
                      Comprehensive characterization of the JUNB-deficient tumor
                      microenvironment revealed a strong influx of myeloid cells
                      into primary breast tumors and lungs at early metastatic
                      stage. In these infiltrating neutrophils, BV8 and MMP9,
                      proteins promoting angiogenesis and tissue remodeling, were
                      specifically upregulated in a JUNB-dependent manner. Taken
                      together, we established stromal JUNB as a strong suppressor
                      of distant metastasis. Consequently, therapeutic strategies
                      targeting AP-1 should be carefully designed not to interfere
                      with stromal JUNB expression as this may be detrimental for
                      cancer patients.},
      keywords     = {Metastasis (Other) / Transcription factor (Other) / Tumor
                      microenvironment (Other)},
      cin          = {A100 / E221},
      ddc          = {610},
      cid          = {I:(DE-He78)A100-20160331 / I:(DE-He78)E221-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34282521},
      doi          = {10.1007/s10585-021-10108-9},
      url          = {https://inrepo02.dkfz.de/record/169894},
}