Title :

Metabolic fingerprinting links oncogenic pik3ca with enhanced arachidonic acid-derived eicosanoids

Author(s) :

Koundouros, Nikos [Auteur]
Imperial College London
Karali, Evdoxia [Auteur]
The institute of cancer research [London]
Tripp, Aurelien [Auteur]
The institute of cancer research [London]
Valle, Adamo [Auteur]
The institute of cancer research [London]
Inglese, Paolo [Auteur]
Imperial College London
Perry, Nicholas J. S. [Auteur]
The institute of cancer research [London]
Magee, David J. [Auteur]
The institute of cancer research [London]
Virmouni, Sara Anjomani [Auteur]
The institute of cancer research [London]
Elder, George A. [Auteur]
The institute of cancer research [London]
Tyson, Adam L. [Auteur]
The institute of cancer research [London]
Doria, Maria Luisa [Auteur]
Imperial College London
Van Weverwijk, Antoinette [Auteur]
The institute of cancer research [London]
Soares, Renata F. [Auteur]
Imperial College London
Isacke, Clare M. [Auteur]
The institute of cancer research [London]
Nicholson, Jeremy K. [Auteur]
Imperial College London
Glen, Robert C. [Auteur]
Imperial College London
Takats, Zoltan [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Poulogiannis, George [Auteur]
The institute of cancer research [London]

Journal title :

Cell

Abbreviated title :

Cell

Volume number :

181

Pages :

1596-1611.e27

Publisher :

Elsevier

Publication date :

2020-06-25

ISSN :

0092-8674

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 iKnife ...
Show more >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 iKnife 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-PKCzeta-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. VIDEO ABSTRACT.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T13:57:55Z
2023-04-05T09:03:57Z
2024-02-14T07:12:57Z