2026-04-29T04:08:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/228742024-11-29T06:44:25Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud
author
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
2024-09-13T09:11:47Z
2024-09-13T09:11:47Z
2020-06-25
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
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.
eng
Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids
research article