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Perspective: Potential Impact and Therapeutic Implications of Oncogenic PI3K Activation on Chromosomal Instability.

Vanhaesebroeck B, Bilanges B, Madsen RR, Dale KL, Lau E, Vladimirou E.

Biomolecules. 2019 Aug 1;9(8). pii: E331. doi: 10.3390/biom9080331. Review.


p110δ PI 3-kinase inhibition perturbs APP and TNFα trafficking, reduces plaque burden, dampens neuroinflammation and prevents cognitive decline in an Alzheimer's disease mouse model.

Martínez-Mármol R, Mohannak N, Qian L, Wang T, Gormal RS, Ruitenberg MJ, Vanhaesebroeck B, Coulson EJ, Meunier FA.

J Neurosci. 2019 Jul 30. pii: 0674-19. doi: 10.1523/JNEUROSCI.0674-19.2019. [Epub ahead of print]


PI3K isoforms in cell signalling and vesicle trafficking.

Bilanges B, Posor Y, Vanhaesebroeck B.

Nat Rev Mol Cell Biol. 2019 Sep;20(9):515-534. doi: 10.1038/s41580-019-0129-z. Review.


Inhibition of PI3Kinase-α is pro-arrhythmic and associated with enhanced late Na+ current, contractility, and Ca2+ release in murine hearts.

Zhabyeyev P, McLean B, Chen X, Vanhaesebroeck B, Oudit GY.

J Mol Cell Cardiol. 2019 Jul;132:98-109. doi: 10.1016/j.yjmcc.2019.05.008. Epub 2019 May 13.


PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.

McLean BA, Patel VB, Zhabyeyev P, Chen X, Basu R, Wang F, Shah S, Vanhaesebroeck B, Oudit GY.

J Am Heart Assoc. 2019 May 7;8(9):e010961. doi: 10.1161/JAHA.118.010961.


Oncogenic PIK3CA promotes cellular stemness in an allele dose-dependent manner.

Madsen RR, Knox RG, Pearce W, Lopez S, Mahler-Araujo B, McGranahan N, Vanhaesebroeck B, Semple RK.

Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8380-8389. doi: 10.1073/pnas.1821093116. Epub 2019 Apr 4.


Targeting PI3Kδ function for amelioration of murine chronic graft-versus-host disease.

Paz K, Flynn R, Du J, Tannheimer S, Johnson AJ, Dong S, Stark AK, Okkenhaug K, Panoskaltsis-Mortari A, Sage PT, Sharpe AH, Luznik L, Ritz J, Soiffer RJ, Cutler CS, Koreth J, Antin JH, Miklos DB, MacDonald KP, Hill GR, Maillard I, Serody JS, Murphy WJ, Munn DH, Feser C, Zaiken M, Vanhaesebroeck B, Turka LA, Byrd JC, Blazar BR.

Am J Transplant. 2019 Jun;19(6):1820-1830. doi: 10.1111/ajt.15305. Epub 2019 Mar 19.


PI3Kα-regulated gelsolin activity is a critical determinant of cardiac cytoskeletal remodeling and heart disease.

Patel VB, Zhabyeyev P, Chen X, Wang F, Paul M, Fan D, McLean BA, Basu R, Zhang P, Shah S, Dawson JF, Pyle WG, Hazra M, Kassiri Z, Hazra S, Vanhaesebroeck B, McCulloch CA, Oudit GY.

Nat Commun. 2018 Dec 19;9(1):5390. doi: 10.1038/s41467-018-07812-8.


Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodelling in response to ischaemic injury.

Chen X, Zhabyeyev P, Azad AK, Wang W, Minerath RA, DesAulniers J, Grueter CE, Murray AG, Kassiri Z, Vanhaesebroeck B, Oudit GY.

Cardiovasc Res. 2019 Jul 1;115(8):1343-1356. doi: 10.1093/cvr/cvy298.


Impact of PI3Kα (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis.

Laurent PA, Hechler B, Solinhac R, Ragab A, Cabou C, Anquetil T, Severin S, Denis CV, Mangin PH, Vanhaesebroeck B, Payrastre B, Gratacap MP.

Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2041-2053. doi: 10.1161/ATVBAHA.118.311410.


Vps34/PI3KC3 deletion in kidney proximal tubules impairs apical trafficking and blocks autophagic flux, causing a Fanconi-like syndrome and renal insufficiency.

Grieco G, Janssens V, Gaide Chevronnay HP, N'Kuli F, Van Der Smissen P, Wang T, Shan J, Vainio S, Bilanges B, Jouret F, Vanhaesebroeck B, Pierreux CE, Courtoy PJ.

Sci Rep. 2018 Sep 20;8(1):14133. doi: 10.1038/s41598-018-32389-z.


Cancer-Associated PIK3CA Mutations in Overgrowth Disorders.

Madsen RR, Vanhaesebroeck B, Semple RK.

Trends Mol Med. 2018 Oct;24(10):856-870. doi: 10.1016/j.molmed.2018.08.003. Epub 2018 Sep 6. Review.


Lessons for cancer drug treatment from tackling a non-cancerous overgrowth syndrome.

Semple RK, Vanhaesebroeck B.

Nature. 2018 Jun;558(7711):523-525. doi: 10.1038/d41586-018-05365-w. No abstract available.


Loss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell transformation via PI3K pathway.

Palam LR, Mali RS, Ramdas B, Srivatsan SN, Visconte V, Tiu RV, Vanhaesebroeck B, Roers A, Gerbaulet A, Xu M, Janga SC, Takemoto CM, Paczesny S, Kapur R.

JCI Insight. 2018 Feb 22;3(4). pii: 94679. doi: 10.1172/jci.insight.94679. eCollection 2018 Feb 22.


Determinants and clinical implications of chromosomal instability in cancer.

Sansregret L, Vanhaesebroeck B, Swanton C.

Nat Rev Clin Oncol. 2018 Mar;15(3):139-150. doi: 10.1038/nrclinonc.2017.198. Epub 2018 Jan 3. Review.


Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism.

Bilanges B, Alliouachene S, Pearce W, Morelli D, Szabadkai G, Chung YL, Chicanne G, Valet C, Hill JM, Voshol PJ, Collinson L, Peddie C, Ali K, Ghazaly E, Rajeeve V, Trichas G, Srinivas S, Chaussade C, Salamon RS, Backer JM, Scudamore CL, Whitehead MA, Keaney EP, Murphy LO, Semple RK, Payrastre B, Tooze SA, Vanhaesebroeck B.

Nat Commun. 2017 Nov 27;8(1):1804. doi: 10.1038/s41467-017-01969-4.


Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling.

Berenjeno IM, Piñeiro R, Castillo SD, Pearce W, McGranahan N, Dewhurst SM, Meniel V, Birkbak NJ, Lau E, Sansregret L, Morelli D, Kanu N, Srinivas S, Graupera M, Parker VER, Montgomery KG, Moniz LS, Scudamore CL, Phillips WA, Semple RK, Clarke A, Swanton C, Vanhaesebroeck B.

Nat Commun. 2017 Nov 24;8(1):1773. doi: 10.1038/s41467-017-02002-4.


The role of PI3Kα isoform in cardioprotection.

Rossello X, Riquelme JA, He Z, Taferner S, Vanhaesebroeck B, Davidson SM, Yellon DM.

Basic Res Cardiol. 2017 Oct 17;112(6):66. doi: 10.1007/s00395-017-0657-7.


A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth.

Valet C, Levade M, Chicanne G, Bilanges B, Cabou C, Viaud J, Gratacap MP, Gaits-Iacovoni F, Vanhaesebroeck B, Payrastre B, Severin S.

Blood. 2017 Nov 2;130(18):2032-2042. doi: 10.1182/blood-2017-04-781641. Epub 2017 Sep 13.


Inhibition of p110δ PI3K prevents inflammatory response and restenosis after artery injury.

Bilancio A, Rinaldi B, Oliviero MA, Donniacuo M, Monti MG, Boscaino A, Marino I, Friedman L, Rossi F, Vanhaesebroeck B, Migliaccio A.

Biosci Rep. 2017 Sep 27;37(5). pii: BSR20171112. doi: 10.1042/BSR20171112. Print 2017 Oct 31.


Phosphoproteomic comparison of Pik3ca and Pten signalling identifies the nucleotidase NT5C as a novel AKT substrate.

Moniz LS, Surinova S, Ghazaly E, Velasco LG, Haider S, Rodríguez-Prados JC, Berenjeno IM, Chelala C, Vanhaesebroeck B.

Sci Rep. 2017 Jan 6;7:39985. doi: 10.1038/srep39985.


Phosphoinositide 3-kinase: a new kid on the block in vascular anomalies.

Castillo SD, Vanhaesebroeck B, Sebire NJ.

J Pathol. 2016 Dec;240(4):387-396. doi: 10.1002/path.4802. Epub 2016 Oct 20. Review.


Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy.

Okkenhaug K, Graupera M, Vanhaesebroeck B.

Cancer Discov. 2016 Oct;6(10):1090-1105. Epub 2016 Sep 21. Review.


Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, Goodlad JR, Farmer G, Steele CL, Leahy TR, Doffinger R, Baxendale H, Bernatoniene J, Edgar JD, Longhurst HJ, Ehl S, Speckmann C, Grimbacher B, Sediva A, Milota T, Faust SN, Williams AP, Hayman G, Kucuk ZY, Hague R, French P, Brooker R, Forsyth P, Herriot R, Cancrini C, Palma P, Ariganello P, Conlon N, Feighery C, Gavin PJ, Jones A, Imai K, Ibrahim MA, Markelj G, Abinun M, Rieux-Laucat F, Latour S, Pellier I, Fischer A, Touzot F, Casanova JL, Durandy A, Burns SO, Savic S, Kumararatne DS, Moshous D, Kracker S, Vanhaesebroeck B, Okkenhaug K, Picard C, Nejentsev S, Condliffe AM, Cant AJ.

J Allergy Clin Immunol. 2017 Feb;139(2):597-606.e4. doi: 10.1016/j.jaci.2016.06.021. Epub 2016 Jul 16.


Inactivation of class II PI3K-C2α induces leptin resistance, age-dependent insulin resistance and obesity in male mice.

Alliouachene S, Bilanges B, Chaussade C, Pearce W, Foukas LC, Scudamore CL, Moniz LS, Vanhaesebroeck B.

Diabetologia. 2016 Jul;59(7):1503-1512. doi: 10.1007/s00125-016-3963-y. Epub 2016 Apr 30.


Corrigendum: Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.

Ali K, Soond DR, Piñeiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H, Friedman L, Turner M, Okkenhaug K, Vanhaesebroeck B.

Nature. 2016 Jul 28;535(7613):580. doi: 10.1038/nature17641. Epub 2016 Apr 6. No abstract available.


Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.

Ang JE, Pandher R, Ang JC, Asad YJ, Henley AT, Valenti M, Box G, de Haven Brandon A, Baird RD, Friedman L, Derynck M, Vanhaesebroeck B, Eccles SA, Kaye SB, Workman P, de Bono JS, Raynaud FI.

Mol Cancer Ther. 2016 Jun;15(6):1412-24. doi: 10.1158/1535-7163.MCT-15-0815. Epub 2016 Apr 5.


Somatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans.

Castillo SD, Tzouanacou E, Zaw-Thin M, Berenjeno IM, Parker VE, Chivite I, Milà-Guasch M, Pearce W, Solomon I, Angulo-Urarte A, Figueiredo AM, Dewhurst RE, Knox RG, Clark GR, Scudamore CL, Badar A, Kalber TL, Foster J, Stuckey DJ, David AL, Phillips WA, Lythgoe MF, Wilson V, Semple RK, Sebire NJ, Kinsler VA, Graupera M, Vanhaesebroeck B.

Sci Transl Med. 2016 Mar 30;8(332):332ra43. doi: 10.1126/scitranslmed.aad9982.


The class I phosphoinositide 3-kinases α and β control antiphospholipid antibodies-induced platelet activation.

Terrisse AD, Laurent PA, Garcia C, Gratacap MP, Vanhaesebroeck B, Sié P, Payrastre B.

Thromb Haemost. 2016 Jun 2;115(6):1138-46. doi: 10.1160/TH15-08-0661. Epub 2016 Jan 28.


Molecules in medicine mini-review: isoforms of PI3K in biology and disease.

Vanhaesebroeck B, Whitehead MA, Piñeiro R.

J Mol Med (Berl). 2016 Jan;94(1):5-11. doi: 10.1007/s00109-015-1352-5. Epub 2015 Dec 10. Review.


Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity.

Alliouachene S, Bilanges B, Chicanne G, Anderson KE, Pearce W, Ali K, Valet C, Posor Y, Low PC, Chaussade C, Scudamore CL, Salamon RS, Backer JM, Stephens L, Hawkins PT, Payrastre B, Vanhaesebroeck B.

Cell Rep. 2015 Dec 1;13(9):1881-94. doi: 10.1016/j.celrep.2015.10.052. Epub 2015 Nov 19.


Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells.

Guillermet-Guibert J, Smith LB, Halet G, Whitehead MA, Pearce W, Rebourcet D, León K, Crépieux P, Nock G, Strömstedt M, Enerback M, Chelala C, Graupera M, Carroll J, Cosulich S, Saunders PT, Huhtaniemi I, Vanhaesebroeck B.

PLoS Genet. 2015 Jul 1;11(7):e1005304. doi: 10.1371/journal.pgen.1005304. eCollection 2015 Jul.


Essential role of class II PI3K-C2α in platelet membrane morphology.

Valet C, Chicanne G, Severac C, Chaussade C, Whitehead MA, Cabou C, Gratacap MP, Gaits-Iacovoni F, Vanhaesebroeck B, Payrastre B, Severin S.

Blood. 2015 Aug 27;126(9):1128-37. doi: 10.1182/blood-2015-03-636670. Epub 2015 Jun 24.


PI3Kα is essential for the recovery from Cre/tamoxifen cardiotoxicity and in myocardial insulin signalling but is not required for normal myocardial contractility in the adult heart.

McLean BA, Zhabyeyev P, Patel VB, Basu R, Parajuli N, DesAulniers J, Murray AG, Kassiri Z, Vanhaesebroeck B, Oudit GY.

Cardiovasc Res. 2015 Mar 1;105(3):292-303. doi: 10.1093/cvr/cvv016. Epub 2015 Jan 24.


Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization.

Peng J, Awad A, Sar S, Komaiha OH, Moyano R, Rayal A, Samuel D, Shewan A, Vanhaesebroeck B, Mostov K, Gassama-Diagne A.

Nat Commun. 2015 Jan 13;6:5937. doi: 10.1038/ncomms6937.


Pancreatic cell plasticity and cancer initiation induced by oncogenic Kras is completely dependent on wild-type PI 3-kinase p110α.

Baer R, Cintas C, Dufresne M, Cassant-Sourdy S, Schönhuber N, Planque L, Lulka H, Couderc B, Bousquet C, Garmy-Susini B, Vanhaesebroeck B, Pyronnet S, Saur D, Guillermet-Guibert J.

Genes Dev. 2014 Dec 1;28(23):2621-35. doi: 10.1101/gad.249409.114.


Platelet PI3Kβ and GSK3 regulate thrombus stability at a high shear rate.

Laurent PA, Séverin S, Hechler B, Vanhaesebroeck B, Payrastre B, Gratacap MP.

Blood. 2015 Jan 29;125(5):881-8. doi: 10.1182/blood-2014-07-588335. Epub 2014 Nov 14.


Cinderella finds her shoe: the first Vps34 inhibitor uncovers a new PI3K-AGC protein kinase connection.

Bilanges B, Vanhaesebroeck B.

Biochem J. 2014 Dec 1;464(2):e7-10. doi: 10.1042/BJ20141218.


A new TIPE of phosphoinositide regulator in cancer.

Moniz LS, Vanhaesebroeck B.

Cancer Cell. 2014 Oct 13;26(4):443-4. doi: 10.1016/j.ccell.2014.09.017.


Phosphoinositide 3-kinase β mediates microvascular endothelial repair of thrombotic microangiopathy.

Haddad G, Zhabyeyev P, Farhan M, Zhu LF, Kassiri Z, Rayner DC, Vanhaesebroeck B, Oudit GY, Murray AG.

Blood. 2014 Sep 25;124(13):2142-9. doi: 10.1182/blood-2014-02-557975. Epub 2014 Aug 18.


Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.

Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, Bouabe H, Scudamore CL, Hancox T, Maecker H, Friedman L, Turner M, Okkenhaug K, Vanhaesebroeck B.

Nature. 2014 Jun 19;510(7505):407-411. doi: 10.1038/nature13444. Epub 2014 Jun 11. Erratum in: Nature. 2016 Jul 28;535(7613):580.


Phosphoinositide 3-kinases p110α and p110β have differential roles in insulin-like growth factor-1-mediated Akt phosphorylation and platelet priming.

Blair TA, Moore SF, Williams CM, Poole AW, Vanhaesebroeck B, Hers I.

Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1681-8. doi: 10.1161/ATVBAHA.114.303954. Epub 2014 Jun 5.


The phosphoinositide 3-kinase isoform PI3Kβ regulates osteoclast-mediated bone resorption in humans and mice.

Győri D, Csete D, Benkő S, Kulkarni S, Mandl P, Dobó-Nagy C, Vanhaesebroeck B, Stephens L, Hawkins PT, Mócsai A.

Arthritis Rheumatol. 2014 Aug;66(8):2210-21. doi: 10.1002/art.38660.


PI3Kδ inhibition hits a sensitive spot in B cell malignancies.

Vanhaesebroeck B, Khwaja A.

Cancer Cell. 2014 Mar 17;25(3):269-71. doi: 10.1016/j.ccr.2014.02.012.


PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model.

Low PC, Manzanero S, Mohannak N, Narayana VK, Nguyen TH, Kvaskoff D, Brennan FH, Ruitenberg MJ, Gelderblom M, Magnus T, Kim HA, Broughton BR, Sobey CG, Vanhaesebroeck B, Stow JL, Arumugam TV, Meunier FA.

Nat Commun. 2014 Mar 14;5:3450. doi: 10.1038/ncomms4450.


PI3K p110δ uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML.

Goodwin CB, Li XJ, Mali RS, Chan G, Kang M, Liu Z, Vanhaesebroeck B, Neel BG, Loh ML, Lannutti BJ, Kapur R, Chan RJ.

Blood. 2014 May 1;123(18):2838-42. doi: 10.1182/blood-2013-10-535104. Epub 2014 Feb 19.


Environmental stress affects the activity of metabolic and growth factor signaling networks and induces autophagy markers in MCF7 breast cancer cells.

Casado P, Bilanges B, Rajeeve V, Vanhaesebroeck B, Cutillas PR.

Mol Cell Proteomics. 2014 Mar;13(3):836-48. doi: 10.1074/mcp.M113.034751. Epub 2014 Jan 14.


Inhibition of the p110α isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis.

Soler A, Serra H, Pearce W, Angulo A, Guillermet-Guibert J, Friedman LS, Viñals F, Gerhardt H, Casanovas O, Graupera M, Vanhaesebroeck B.

J Exp Med. 2013 Sep 23;210(10):1937-45. doi: 10.1084/jem.20121571. Epub 2013 Sep 16.


Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells.

Rajasekaran K, Kumar P, Schuldt KM, Peterson EJ, Vanhaesebroeck B, Dixit V, Thakar MS, Malarkannan S.

Nat Immunol. 2013 Nov;14(11):1127-36. doi: 10.1038/ni.2708. Epub 2013 Sep 15. Erratum in: Nat Immunol. 2014 Feb;15(2):205.


AKT-ing out: SGK kinases come to the fore.

Moniz LS, Vanhaesebroeck B.

Biochem J. 2013 Jun 15;452(3):e11-3. doi: 10.1042/BJ20130617.


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