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@ARTICLE{Kong:285439,
      author       = {Y. Kong and Y. Liu and X. Li$^*$ and M. Rao and D. Li and
                      X. Ruan and S. Li and Z. Jiang and Q. Zhang},
      title        = {{P}almitoylation landscapes across human cancers reveal a
                      role of palmitoylation in tumorigenesis.},
      journal      = {Journal of translational medicine},
      volume       = {21},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-02373},
      pages        = {826},
      year         = {2023},
      note         = {#EA:C070#},
      abstract     = {Protein palmitoylation, which is catalyzed by
                      palmitoyl-transferase and de-palmitoyl-transferase, plays a
                      crucial role in various biological processes. However, the
                      landscape and dynamics of protein palmitoylation in human
                      cancers are not well understood.We utilized 23
                      palmitoyl-acyltransferases and seven
                      de-palmitoyl-acyltransferases as palmitoylation-related
                      genes for protein palmitoylation analysis. Multiple publicly
                      available datasets were employed to conduct pan-cancer
                      analysis, examining the transcriptome, genomic alterations,
                      clinical outcomes, and correlation with c-Myc (Myc) for
                      palmitoylation-related genes. Real-time quantitative PCR and
                      immunoblotting were performed to assess the expression of
                      palmitoylation-related genes and global protein
                      palmitoylation levels in cancer cells treated with Myc
                      depletion or small molecule inhibitors. Protein docking and
                      drug sensitivity analyses were employed to predict small
                      molecules that target palmitoylation-related genes.We
                      identified associations between palmitoylation and cancer
                      subtype, stage, and patient survival. We discovered that
                      abnormal DNA methylation and oncogenic Myc-driven
                      transcriptional regulation synergistically contribute to the
                      dysregulation of palmitoylation-related genes. This
                      dysregulation of palmitoylation was closely correlated with
                      immune infiltration in the tumor microenvironment and the
                      response to immunotherapy. Importantly, dysregulated
                      palmitoylation was found to modulate canonical
                      cancer-related pathways, thus influencing tumorigenesis. To
                      support our findings, we performed a proof-of-concept
                      experiment showing that depletion of Myc led to reduced
                      expression of most palmitoylation-related genes, resulting
                      in decreased global protein palmitoylation levels. Through
                      mass spectrometry and enrichment analyses, we also
                      identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as
                      significant contributors to mTOR signaling, DNA repair, and
                      immune pathways, highlighting their potential roles in
                      tumorigenesis. Additionally, our study explored the
                      potential of three small molecular (BI-2531, etoposide, and
                      piperlongumine) to modulate palmitoylation by targeting the
                      expression or activity of palmitoylation-related genes or
                      enzymes.Overall, our findings underscore the critical role
                      of dysregulated palmitoylation in tumorigenesis and the
                      response to immunotherapy, mediated through classical
                      cancer-related pathways and immune cell infiltration.
                      Additionally, we propose that the aforementioned three small
                      molecule hold promise as potential therapeutics for
                      modulating palmitoylation, thereby offering novel avenues
                      for cancer therapy.},
      keywords     = {Cancer (Other) / DNA methylation (Other) / Immunotherapy
                      (Other) / Palmitoylation (Other) / Small molecular (Other) /
                      c-Myc (Other)},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37978524},
      pmc          = {pmc:PMC10655258},
      doi          = {10.1186/s12967-023-04611-8},
      url          = {https://inrepo02.dkfz.de/record/285439},
}