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000304285 1001_ $$00000-0002-4075-7820$$aColeman, Olivia I$$b0
000304285 245__ $$aATF6 activation alters colonic lipid metabolism causing tumour-associated microbial adaptation.
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000304285 520__ $$aEndoplasmic reticulum unfolded protein responses contribute to cancer development, with activating transcription factor 6 (ATF6) involved in microbiota-dependent tumorigenesis. Here we show the clinical relevance of ATF6 in individuals with early-onset and late colorectal cancer, and link ATF6 signalling to changes in lipid metabolism and intestinal microbiota. Transcriptional analysis in intestinal epithelial cells of ATF6 transgenic mice (nATF6IEC) identifies bacteria-specific changes in cellular metabolism enriched for fatty acid biosynthesis. Untargeted metabolomics and isotype labelling confirm ATF6-related enrichment of long-chain fatty acids in colonic tissue of humans, mice and organoids. FASN inhibition and microbiota transfer in germ-free nATF6IEC mice confirm the causal involvement of ATF6-induced lipid alterations in tumorigenesis. The selective expansion of tumour-relevant microbial taxa, including Desulfovibrio fairfieldensis, is mechanistically linked to long-chain fatty acid exposure using bioorthogonal non-canonical amino acid tagging, and growth analysis of Desulfovibrio isolates. We postulate chronic ATF6 signalling to select for tumour-promoting microbiota by altering lipid metabolism.
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000304285 7001_ $$00000-0002-3330-4612$$aSorbie, Adam$$b1
000304285 7001_ $$00000-0002-5724-7616$$aRiva, Alessandra$$b2
000304285 7001_ $$avon Stern, Miriam$$b3
000304285 7001_ $$aKuhls, Stephanie$$b4
000304285 7001_ $$aSelegato, Denise M$$b5
000304285 7001_ $$aSiegert, Luisa$$b6
000304285 7001_ $$00009-0000-9806-1087$$aKeidel, Isabel$$b7
000304285 7001_ $$00000-0002-5103-883X$$aKöhler, Nikolai$$b8
000304285 7001_ $$00000-0002-4073-3562$$aWirbel, Jakob$$b9
000304285 7001_ $$00000-0002-5393-2413$$aKacprowski, Tim$$b10
000304285 7001_ $$aDunkel, Andreas$$b11
000304285 7001_ $$aPauling, Josch K$$b12
000304285 7001_ $$aPlagge, Johannes$$b13
000304285 7001_ $$aMediel-Cuadra, Diego$$b14
000304285 7001_ $$aWagner, Sophia J$$b15
000304285 7001_ $$aChadly, Ines$$b16
000304285 7001_ $$aBierwith, Sandra$$b17
000304285 7001_ $$aPeng, Tingying$$b18
000304285 7001_ $$00000-0002-1620-5559$$aMetzler, Thomas$$b19
000304285 7001_ $$0P:(DE-He78)0d56bfbd4cd4cf94f34df200f9d9f7c1$$aLi, Xin-Feng$$b20
000304285 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b21$$udkfz
000304285 7001_ $$aSchafmayer, Clemens$$b22
000304285 7001_ $$aHinz, Sebastian$$b23
000304285 7001_ $$aRöder, Christian$$b24
000304285 7001_ $$aRöcken, Christoph$$b25
000304285 7001_ $$00000-0002-5797-3589$$aZimmermann, Michael$$b26
000304285 7001_ $$00000-0002-9692-8828$$aRosenstiel, Philip$$b27
000304285 7001_ $$aSteiger, Katja$$b28
000304285 7001_ $$aJesinghaus, Moritz$$b29
000304285 7001_ $$00000-0003-4886-0811$$aLiebisch, Gerhard$$b30
000304285 7001_ $$00000-0003-4799-0788$$aEcker, Josef$$b31
000304285 7001_ $$00000-0002-3867-0881$$aSchmidt, Christina$$b32
000304285 7001_ $$aZeller, Georg$$b33
000304285 7001_ $$00000-0002-4707-7887$$aJanssen, Klaus-Peter$$b34
000304285 7001_ $$00000-0002-6977-4085$$aHaller, Dirk$$b35
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