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@ARTICLE{Kim:182712,
      author       = {M. Kim$^*$ and S. Reidenbach$^*$ and T. Schlechter$^*$ and
                      A. C. Rothmann$^*$ and R. Will$^*$ and I. Hofmann$^*$},
      title        = {{P}lakophilin 1 deficiency in prostatic tumors is
                      correlated with immune cell recruitment and controls the
                      up-regulation of cytokine expression
                      post-transcriptionally.},
      journal      = {The FEBS journal},
      volume       = {290},
      number       = {7},
      issn         = {0014-2956},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2022-02870},
      pages        = {1907-1919},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance / #EA:A190#LA:A190# / 2023
                      Apr;290(7):1907-1919},
      abstract     = {Plakophilin (PKP1) 1 is a member of the arm-repeat family
                      of catenins and acts as structural component of desmosomes,
                      which are important stabilizers of cell-cell adhesion.
                      Besides this, PKP1 also occurs in a non-junctional,
                      cytoplasmic form contributing to post-transcriptional
                      regulation of gene expression. Moreover, PKP1 is expressed
                      in prostate epithelium but its expression is frequently
                      downregulated in prostate cancers with a more aggressive
                      phenotype. This observation may imply a tumor-suppressive
                      role of PKP1. We found that, in prostatic adenocarcinomas
                      with PKP1 deficiency, the occurrence of T-cells, B-cells,
                      macrophages and neutrophils was significantly increased. In
                      a PKP1-deficient prostatic cancer cell line expressing IL8,
                      these levels were statistically meaningfully reduced upon
                      PKP1 re-expression. When analyzing prostatic PKP1-knockdown
                      cell lines, the mRNA and protein levels of additional
                      cytokines, namely CXCL1 and IL6, were upregulated. The
                      effect was rescued upon re-expression of a PKP1
                      RNAi-resistant form. The corresponding mRNAs were
                      co-precipitated with cytoplasmic PKP1, indicating that they
                      are components of PKP1-containing mRNA ribonucleoprotein
                      particles. Moreover, the mRNA half-lives of CXCL1, IL8 and
                      IL6 were significantly increased in PKP1-deficient cells,
                      showing that these mRNAs were stabilized by PKP1. In an in
                      vitro migration assay, the higher cytokine concentrations
                      led to higher migration rates of THP1 and PBMC cells. This
                      finding implies that PKP1 loss of expression in vivo
                      correlates with recruitment of immune cells into the tumor
                      area to set up a tumor-specific environment. One may
                      speculate that this newly established tumor environment has
                      tumor-suppressive characteristics and thereby accelerates
                      tumor progression and metastasis.},
      keywords     = {Prostate cancer (Other) / cytokine mRNA stability (Other) /
                      immune cell recruitment (Other) / plakophilin 1 (Other) /
                      tumor environment (Other)},
      cin          = {A190 / W170 / W111},
      ddc          = {610},
      cid          = {I:(DE-He78)A190-20160331 / I:(DE-He78)W170-20160331 /
                      I:(DE-He78)W111-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36380691},
      doi          = {10.1111/febs.16680},
      url          = {https://inrepo02.dkfz.de/record/182712},
}