2026-04-29T04:09:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/228742024-11-29T06:44:25Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Koundouros, Nikos author Karali, Evdoxia author Tripp, Aurelien author Valle, Adamo author Inglese, Paolo author Perry, Nicholas JS author Magee, David J author Virmouni, Sara Anjomani author Elder, George A author Tyson, Adam L author Doria, Maria Luisa author van Weverwijk, Antoinette author Soares, Renata F author Isacke, Clare M author Nicholson, Jeremy K author Glen, Robert C author Takats, Zoltan author Poulogiannis, George author 2020-06-25 Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the 'Knife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKC zeta-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. Koundouros N, Karali E, Tripp A, Valle A, Inglese P, Perry N, et al. Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids. Cell. 2020 Jun 25;181(7):1596-611. Epub 2020 Jun 18. 0092-8674 http://hdl.handle.net/20.500.13003/17241 https://hdl.handle.net/20.500.12105/22874 32559461 10.1016/j.cell.2020.05.053 1097-4172 Cell 2-s2.0-85086742293 543822100016 L2006823274 Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids