title: FADS2 function loss at the cancer hotspot 11q13 locus diverts lipid signaling precursor synthesis to unusual eicosanoid fatty acids.
abstract: BACKGROUND
  Genes coding for the fatty acid desaturases (FADS1, 2, 3) localized at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20 carbon polyunsaturated fatty acids (PUFA) that are direct eicosanoid precursors. In several cancer cell lines, FADS2 encoded Δ6 and Δ8 desaturation is not functional.
  
  
  RESULTS
  Analyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product Δ5-desaturase operates to produce 5,11,14-20∶3 and 5,11,14,17-20∶4. These PUFA are missing the 8-9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14-20∶4) and eicosapentaenoic acid (5,8,11,14,17-20∶5). Heterologous expression of FADS2 restores Δ6 and Δ8-desaturase activity and normal eicosanoid precursor synthesis.
  
  
  CONCLUSIONS
  The loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States of America.
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Park
authors.forename: Kumar S D
authors.initials: KS
authors.lastname: Kothapalli
authors.forename: Peter
authors.initials: P
authors.lastname: Lawrence
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Brenna
mesh_terms: D045744:Cell Line, Tumor; D002849:Chromatography, Gas; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D000090943:Delta-5 Fatty Acid Desaturase; D015777:Eicosanoids / Q000096:biosynthesis*; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D015777:Eicosanoids; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human