X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.

Nikos Koundouros | Evdoxia Karali | Aurelien Tripp | Adamo Valle | Paolo Inglese | Nicholas J S Perry | David J Magee | Sara Anjomani Virmouni | George A Elder | Adam L Tyson | Maria Luisa Dória | Antoinette van Weverwijk | Renata F Soares | Clare M Isacke | Jeremy K Nicholson | Robert C Glen | Zoltan Takats | George Poulogiannis
Cell | 2020

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-PKCζ-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.

Pubmed ID: 32559461 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

  • Agency: Cancer Research UK, United Kingdom
    Id: C59824/A25044

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


MATLAB (tool)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

View all literature mentions

ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

View all literature mentions

DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

View all literature mentions

R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

View all literature mentions

Mendeley Data (tool)

RRID:SCR_002750

A free reference manager and academic social network to organize your research, collaborate with others online, and discover the latest research. Automatically generate bibliographies, Collaborate easily with other researchers online, Easily import papers from other research software, Find relevant papers based on what you're reading, Access your papers from anywhere online, Read papers on the go with the iPhone app. The software, Mendeley Desktop, offers: * Automatic extraction of document details * Efficient management of your papers * Sharing and synchronization of your library (or parts of it) * Additional features: A plug-in for citing your articles in Microsoft Word, OCR (image-to-text conversion, so you can full-text search all your scanned PDFs), etc The website, Mendeley Web, complements Mendeley Desktop by offering these features: * An online back up of your library * Statistics of all things interesting * A research network that allows you to keep track of your colleagues' publications, conference participations, awards etc * A recommendation engine for papers that might interest you

View all literature mentions

Sino Biological (tool)

RRID:SCR_003697

An Antibody supplier

View all literature mentions

Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

View all literature mentions

LIPID Metabolites And Pathways Strategy (tool)

RRID:SCR_006579

A multi-institutional effort to identify and quantitate, using a systems biology approach and sophisticated mass spectrometers, all of the major - and many minor - lipid species in mammalian cells, as well as to quantitate the changes in these species in response to perturbation. The goal of their research is to better understand lipid metabolism and the active role lipids play in diabetes, stroke, cancer, arthritis, Alzheimer's and other lipid-based diseases in order to facilitate development of more effective treatments. Resources available include: LIPID MAPS publications, detailed biochemical pathways, improved protocols for lipid separation and quantification, analytical tools for determining lipid quantitation, structure drawing tools for automatically drawing lipid molecular structures in stereochemical detail, and experimental data. The LIPID MAPS organization includes six lipidomics core laboratories, each specialized in extracting, identifying, and quantifying one of the major categories of mammalian lipids: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and prenol lipids. Other core laboratories and bridge projects include bioinformatics, mass spectrometric imaging, lipid synthesis, oxidized lipids, and macrophage biology and genomics.

View all literature mentions

Promega (tool)

RRID:SCR_006724

An Antibody supplier

View all literature mentions

PeproTech (tool)

RRID:SCR_006802

An Antibody supplier

View all literature mentions

QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

View all literature mentions

Millipore (tool)

RRID:SCR_008983

An Antibody supplier

View all literature mentions

ProteoWizard (tool)

RRID:SCR_012056

Software that enables rapid tool creation by providing a robust, pluggable development framework that simplifies and unifies data file access, and performs standard proteomics and LCMS dataset computations.

View all literature mentions

MCF-10A (tool)

RRID:CVCL_0598

Cell line MCF-10A is a Spontaneously immortalized cell line with a species of origin Homo sapiens

View all literature mentions

BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

View all literature mentions

PLC-gamma-1 Antibody (antibody)

RRID:AB_2163702

This unknown targets PLC gamma 1

View all literature mentions

HA-Tag (C29F4) Rabbit mAb (antibody)

RRID:AB_1549585

This monoclonal targets HA-Tag

View all literature mentions

normal rabbit IgG (antibody)

RRID:AB_737197

This unknown targets normal rabbit IgG

View all literature mentions

p-RKIP (80.Ser 153) (antibody)

RRID:AB_2163163

This monoclonal targets p-RKIP (80.Ser 153)

View all literature mentions

Phospho-cPLA2 (Ser505) Antibody (antibody)

RRID:AB_2164445

This polyclonal targets Pla2g1b

View all literature mentions

4E-BP1 (53H11) Rabbit mAb (antibody)

RRID:AB_2097841

This monoclonal targets 4E-BP1 (53H11) Rabbit mAb

View all literature mentions

cPLA2 Antibody (antibody)

RRID:AB_2164442

This polyclonal targets Pla2g1b

View all literature mentions

Phospho-p38 MAPK (Thr180/Tyr182) Antibody (antibody)

RRID:AB_331641

This polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)

View all literature mentions

p44/42 MAPK (Erk1/2) Antibody (antibody)

RRID:AB_330744

This polyclonal targets p44/42 MAPK (Erk1/2)

View all literature mentions

Ki-67 (D3B5) Rabbit mAb (antibody)

RRID:AB_2687446

This monoclonal targets Ki-67

View all literature mentions

PKC epsilon (phospho S729) antibody (antibody)

RRID:AB_1142277

This polyclonal targets PKC epsilon (phospho S729) antibody

View all literature mentions

mTOR (7C10) Rabbit mAb (antibody)

RRID:AB_2105622

This monoclonal targets mTOR

View all literature mentions

Phospho-MEK1/2 (Ser217/221) Antibody (antibody)

RRID:AB_331648

This polyclonal targets Phospho-MEK1/2 (Ser217/221)

View all literature mentions

Rictor Antibody (antibody)

RRID:AB_2179961

This polyclonal targets Rictor

View all literature mentions

MEK1/2 Antibody (antibody)

RRID:AB_823567

This polyclonal targets MEK1/2

View all literature mentions

Raptor (24C12) Rabbit mAb (antibody)

RRID:AB_561245

This monoclonal targets Raptor (24C12) Rabbit mAb

View all literature mentions

Phospho-c-Raf (Ser338) (56A6) Rabbit mAb (antibody)

RRID:AB_2067317

This monoclonal targets c-Raf, phospho (Ser338)

View all literature mentions

PKC zeta (phospho T560) antibody [EP2037AY] (antibody)

RRID:AB_946309

This monoclonal targets PKC zeta (phospho T560) antibody [EP2037AY]

View all literature mentions

PKD/PKCμ (D4J1N) Rabbit mAb (antibody)

RRID:AB_2800149

This monoclonal targets PRKD1

View all literature mentions

Phospho-NDRG1 (Thr346) (D98G11) XP Rabbit mAb (antibody)

RRID:AB_10693451

This monoclonal targets Phospho-NDRG1 (Thr346) (D98G11) XP Rabbit mAb

View all literature mentions

NDRG1 Antibody (antibody)

RRID:AB_10626626

This polyclonal targets NDRG1

View all literature mentions

Lipocalin 2 antibody (antibody)

RRID:AB_2136471

This polyclonal targets Lipocalin 2 antibody

View all literature mentions

Phospho-S6 Ribosomal Protein (Ser235/236) Antibody (antibody)

RRID:AB_331679

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)

View all literature mentions

Rb (4H1) Mouse mAb (antibody)

RRID:AB_823629

This monoclonal targets Rb (4H1) Mouse mAb

View all literature mentions

Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

View all literature mentions

S6 Ribosomal Protein (54D2) Mouse mAb (antibody)

RRID:AB_2238583

This monoclonal targets S6 Ribosomal Protein (54D2) Mouse mAb

View all literature mentions

Phospho-PKD/PKCmu (Ser744/748) Antibody (antibody)

RRID:AB_2172539

This unknown targets PKD / PKC mu, phospho (Ser744 / Ser748)

View all literature mentions

Goat Anti-Rabbit IgG (H + L)-HRP Conjugate (antibody)

RRID:AB_11125142

This polyclonal secondary targets IgG (H+L)

View all literature mentions

SREBP-1 (antibody)

RRID:AB_396559

This monoclonal targets SREBP-1

View all literature mentions

Phospho-PKC (pan) (βII Ser660) Antibody (antibody)

RRID:AB_2168219

This polyclonal targets Phospho-PKC (pan) (βII Ser660)

View all literature mentions

Phospho-PKC zeta (Thr410) Monoclonal Antibody (S.447.6) (antibody)

RRID:AB_10983263

This monoclonal targets Phospho-PKC zeta (Thr410)

View all literature mentions

Anti-Phospholipase A2 (iPLA2) antibody produced in rabbit (antibody)

RRID:AB_11129638

This polyclonal targets Phospholipase A2 (iPLA2) antibody produced in rabbit

View all literature mentions

Lamin B1 (D4Q4Z) Rabbit mAb #12586 (antibody)

RRID:AB_2650517

This monoclonal targets Lamin B1

View all literature mentions

Phospho-4E-BP1 (Ser65) Antibody (antibody)

RRID:AB_330947

This polyclonal targets Phospho-4E-BP1 (Ser65)

View all literature mentions

Phospho-p70 S6 Kinase (Thr389) Antibody (antibody)

RRID:AB_330944

This polyclonal targets Phospho-p70 S6 Kinase (Thr389)

View all literature mentions

Phospho-Stat3 (Ser727) Antibody (antibody)

RRID:AB_331589

This polyclonal targets Phospho-Stat3 (Ser727)

View all literature mentions

p70 S6 Kinase Antibody (antibody)

RRID:AB_331676

This polyclonal targets p70 S6 Kinase

View all literature mentions

Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)

RRID:AB_2315049

This monoclonal targets Phospho-Akt (Ser473)

View all literature mentions

Stat3 (79D7) Rabbit mAb (antibody)

RRID:AB_331269

This recombinant monoclonal targets Stat3

View all literature mentions

Akt Antibody (antibody)

RRID:AB_329827

This polyclonal targets Akt

View all literature mentions

β-Actin Antibody (antibody)

RRID:AB_330288

This polyclonal targets β-actin

View all literature mentions

Phospho-I B (Ser32) (14D4) Rabbit mAb (antibody)

RRID:AB_561111

This monoclonal targets Phospho-I B (Ser32)

View all literature mentions

Phospho-Threonine/Tyrosine Antibody (antibody)

RRID:AB_330301

This polyclonal targets Phospho-Threonine/Tyrosine

View all literature mentions

Phospho-PLCgamma1 (Tyr783) Antibody (antibody)

RRID:AB_330855

This polyclonal targets Phospho-PLCgamma1 (Tyr783)

View all literature mentions

HCC70 (cell line)

RRID:CVCL_1270

Cell line HCC70 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

CAMA-1 (cell line)

RRID:CVCL_1115

Cell line CAMA-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

CAL-51 (cell line)

RRID:CVCL_1110

Cell line CAL-51 is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

HCC38 (cell line)

RRID:CVCL_1267

Cell line HCC38 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

BT-549 (cell line)

RRID:CVCL_1092

Cell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

BT-474 (cell line)

RRID:CVCL_0179

Cell line BT-474 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC202 (cell line)

RRID:CVCL_2062

Cell line HCC202 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

BT-20 (cell line)

RRID:CVCL_0178

Cell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

AU565 (cell line)

RRID:CVCL_1074

Cell line AU565 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

VP229 (cell line)

RRID:CVCL_2754

Cell line VP229 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1954 (cell line)

RRID:CVCL_1259

Cell line HCC1954 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1937 (cell line)

RRID:CVCL_0290

Cell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

UACC-812 (cell line)

RRID:CVCL_1781

Cell line UACC-812 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1569 (cell line)

RRID:CVCL_1255

Cell line HCC1569 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

T-47D (cell line)

RRID:CVCL_0553

Cell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1500 (cell line)

RRID:CVCL_1254

Cell line HCC1500 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SK-BR-3 (cell line)

RRID:CVCL_0033

Cell line SK-BR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

S68 (cell line)

RRID:CVCL_5585

Cell line S68 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-361 (cell line)

RRID:CVCL_0620

Cell line MDA-MB-361 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1428 (cell line)

RRID:CVCL_1252

Cell line HCC1428 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MFM-223 (cell line)

RRID:CVCL_1408

Cell line MFM-223 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-468 (cell line)

RRID:CVCL_0419

Cell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1395 (cell line)

RRID:CVCL_1249

Cell line HCC1395 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-453 (cell line)

RRID:CVCL_0418

Cell line MDA-MB-453 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-436 (cell line)

RRID:CVCL_0623

Cell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HCC1143 (cell line)

RRID:CVCL_1245

Cell line HCC1143 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

BT-483 (cell line)

RRID:CVCL_2319

Cell line BT-483 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM229PE (cell line)

RRID:CVCL_5594

Cell line SUM229PE is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM225CWN (cell line)

RRID:CVCL_5593

Cell line SUM225CWN is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-231 (cell line)

RRID:CVCL_0062

Cell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-157 (cell line)

RRID:CVCL_0618

Cell line MDA-MB-157 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM149PT (cell line)

RRID:CVCL_3422

Cell line SUM149PT is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM159PT (cell line)

RRID:CVCL_5423

Cell line SUM159PT is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MDA-MB-134-VI (cell line)

RRID:CVCL_0617

Cell line MDA-MB-134-VI is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM44PE (cell line)

RRID:CVCL_3424

Cell line SUM44PE is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MCF-7 (cell line)

RRID:CVCL_0031

Cell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

ZR-75-30 (cell line)

RRID:CVCL_1661

Cell line ZR-75-30 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

KPL-1 (cell line)

RRID:CVCL_2094

Cell line KPL-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

JIMT-1 (cell line)

RRID:CVCL_2077

Cell line JIMT-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

ZR-75-1 (cell line)

RRID:CVCL_0588

Cell line ZR-75-1 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Hs 578T (cell line)

RRID:CVCL_0332

Cell line Hs 578T is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

EFM-19 (cell line)

RRID:CVCL_0253

Cell line EFM-19 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM52PE (cell line)

RRID:CVCL_3425

Cell line SUM52PE is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

SUM44PE (cell line)

RRID:CVCL_3424

Cell line SUM44PE is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions