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@ARTICLE{Coleman:304285,
      author       = {O. I. Coleman and A. Sorbie and A. Riva and M. von Stern
                      and S. Kuhls and D. M. Selegato and L. Siegert and I. Keidel
                      and N. Köhler and J. Wirbel and T. Kacprowski and A. Dunkel
                      and J. K. Pauling and J. Plagge and D. Mediel-Cuadra and S.
                      J. Wagner and I. Chadly and S. Bierwith and T. Peng and T.
                      Metzler and X.-F. Li$^*$ and M. Heikenwälder$^*$ and C.
                      Schafmayer and S. Hinz and C. Röder and C. Röcken and M.
                      Zimmermann and P. Rosenstiel and K. Steiger and M.
                      Jesinghaus and G. Liebisch and J. Ecker and C. Schmidt and
                      G. Zeller and K.-P. Janssen and D. Haller},
      title        = {{ATF}6 activation alters colonic lipid metabolism causing
                      tumour-associated microbial adaptation.},
      journal      = {Nature metabolism},
      volume       = {nn},
      issn         = {2522-5812},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-01825},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Endoplasmic reticulum unfolded protein responses contribute
                      to cancer development, with activating transcription factor
                      6 (ATF6) involved in microbiota-dependent tumorigenesis.
                      Here we show the clinical relevance of ATF6 in individuals
                      with early-onset and late colorectal cancer, and link ATF6
                      signalling to changes in lipid metabolism and intestinal
                      microbiota. Transcriptional analysis in intestinal
                      epithelial cells of ATF6 transgenic mice (nATF6IEC)
                      identifies bacteria-specific changes in cellular metabolism
                      enriched for fatty acid biosynthesis. Untargeted
                      metabolomics and isotype labelling confirm ATF6-related
                      enrichment of long-chain fatty acids in colonic tissue of
                      humans, mice and organoids. FASN inhibition and microbiota
                      transfer in germ-free nATF6IEC mice confirm the causal
                      involvement of ATF6-induced lipid alterations in
                      tumorigenesis. The selective expansion of tumour-relevant
                      microbial taxa, including Desulfovibrio fairfieldensis, is
                      mechanistically linked to long-chain fatty acid exposure
                      using bioorthogonal non-canonical amino acid tagging, and
                      growth analysis of Desulfovibrio isolates. We postulate
                      chronic ATF6 signalling to select for tumour-promoting
                      microbiota by altering lipid metabolism.},
      cin          = {D440},
      ddc          = {610},
      cid          = {I:(DE-He78)D440-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40890536},
      doi          = {10.1038/s42255-025-01350-6},
      url          = {https://inrepo02.dkfz.de/record/304285},
}