PIK3CA

PIK3CA
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ENQ, 2RD0, 3HHM, 3HIZ, 3ZIM, 4JPS, 4L1B, 4L23, 4L2Y, 4OVU, 4OVV, 4TUU, 4TV3, 4WAF, 4YKN, 5DXH, 5DXT, 5FI4, 4ZOP
Identifikatori
Aliasi	PIK3CA
Vanjski ID-jevi	OMIM: 171834 MGI: 1206581 HomoloGene: 21249 GeneCards: PIK3CA
EC broj	2.7.11.1
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	179,240,093 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	32,522,635 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • protein kinase activator activity; • 1-phosphatidylinositol-4-phosphate 3-kinase activity; • protein serine/threonine kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • insulin receptor substrate binding; • ATP binding; • 1-phosphatidylinositol-3-kinase activity; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • kinase activity; • phosphatidylinositol 3-kinase activity; • phosphatidylinositol-3,4-bisphosphate 5-kinase activity;
Ćelijska komponenta	• phosphatidylinositol 3-kinase complex; • citosol; • phosphatidylinositol 3-kinase complex, class IA; • ćelijska membrana; • lamellipodium; • citoplazma; • membrana;
Biološki proces	• GO:1904089 negative regulation of neuron apoptotic process; • cardiac muscle contraction; • epidermal growth factor receptor signaling pathway; • protein kinase B signaling; • Fc-gamma receptor signaling pathway involved in phagocytosis; • regulation of multicellular organism growth; • T cell costimulation; • hypomethylation of CpG island; • positive regulation of peptidyl-serine phosphorylation; • platelet activation; • Fc-epsilon receptor signaling pathway; • phosphatidylinositol phosphate biosynthetic process; • vascular endothelial growth factor receptor signaling pathway; • vasculature development; • Angiogeneza; • insulin receptor signaling pathway via phosphatidylinositol 3-kinase; • glucose metabolic process; • Fagocitoza; • energy homeostasis; • negative regulation of fibroblast apoptotic process; • Regulacija ekspresije gena; • liver development; • adipose tissue development; • regulation of cellular respiration; • T cell receptor signaling pathway; • activation of protein kinase activity; • regulation of genetic imprinting; • negative regulation of anoikis; • cellular response to glucose stimulus; • endothelial cell migration; • phosphatidylinositol-mediated signaling; • leukocyte migration; • ERBB2 signaling pathway; • phosphatidylinositol-3-phosphate biosynthetic process; • axon guidance; • negative regulation of macroautophagy; • Fosforilacija; • positive regulation of TOR signaling; • anoikis; • adaptive immune response; • protein phosphorylation; • inflammatory response; • Urođeni imunski sistem; • cell chemotaxis; • G protein-coupled receptor signaling pathway; • positive regulation of protein kinase B signaling; • phosphatidylinositol 3-kinase signaling; • cytokine-mediated signaling pathway; • Ćelijska migracija; • positive regulation of phosphatidylinositol 3-kinase signaling; • phosphatidylinositol biosynthetic process; • regulation of protein phosphorylation;
	Izvori:Amigo / QuickGO
Ortolozi
	5290
	18706
	ENSG00000121879
	ENSMUSG00000027665
	P42336
	P42337
	NM_006218
	NM_008839
	NP_006209
	NP_032865
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Katalitska podjedinica alfa fosfatidilinozitol-4,5-bisfosfat 3-kinaze (službeni simbol koji je odobrila HUGO = PIK3CA; HGNC ID, HGNC:8975), zvana i protein p110α, jest protein koji je kod ljudi kodiran genom PIK3CA sa hromosoma 3. To je klasa I PI 3-kinaza, katalitskih katalitskih podjedinica. Ljudski p110α protein je kodiran ovim genom.^[5]

Njegovu ulogu otkrila je molekulska patološka epidemiologija (MPE).^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.068 aminokiselina, а molekulska težina 124.284 Da.^[7]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MPPRPSSGEL	WGIHLMPPRI	LVECLLPNGM	IVTLECLREA	TLITIKHELF
KEARKYPLHQ	LLQDESSYIF	VSVTQEAERE	EFFDETRRLC	DLRLFQPFLK
VIEPVGNREE	KILNREIGFA	IGMPVCEFDM	VKDPEVQDFR	RNILNVCKEA
VDLRDLNSPH	SRAMYVYPPN	VESSPELPKH	IYNKLDKGQI	IVVIWVIVSP
NNDKQKYTLK	INHDCVPEQV	IAEAIRKKTR	SMLLSSEQLK	LCVLEYQGKY
ILKVCGCDEY	FLEKYPLSQY	KYIRSCIMLG	RMPNLMLMAK	ESLYSQLPMD
CFTMPSYSRR	ISTATPYMNG	ETSTKSLWVI	NSALRIKILC	ATYVNVNIRD
IDKIYVRTGI	YHGGEPLCDN	VNTQRVPCSN	PRWNEWLNYD	IYIPDLPRAA
RLCLSICSVK	GRKGAKEEHC	PLAWGNINLF	DYTDTLVSGK	MALNLWPVPH
GLEDLLNPIG	VTGSNPNKET	PCLELEFDWF	SSVVKFPDMS	VIEEHANWSV
SREAGFSYSH	AGLSNRLARD	NELRENDKEQ	LKAISTRDPL	SEITEQEKDF
LWSHRHYCVT	IPEILPKLLL	SVKWNSRDEV	AQMYCLVKDW	PPIKPEQAME
LLDCNYPDPM	VRGFAVRCLE	KYLTDDKLSQ	YLIQLVQVLK	YEQYLDNLLV
RFLLKKALTN	QRIGHFFFWH	LKSEMHNKTV	SQRFGLLLES	YCRACGMYLK
HLNRQVEAME	KLINLTDILK	QEKKDETQKV	QMKFLVEQMR	RPDFMDALQG
FLSPLNPAHQ	LGNLRLEECR	IMSSAKRPLW	LNWENPDIMS	ELLFQNNEII
FKNGDDLRQD	MLTLQIIRIM	ENIWQNQGLD	LRMLPYGCLS	IGDCVGLIEV
VRNSHTIMQI	QCKGGLKGAL	QFNSHTLHQW	LKDKNKGEIY	DAAIDLFTRS
CAGYCVATFI	LGIGDRHNSN	IMVKDDGQLF	HIDFGHFLDH	KKKKFGYKRE
RVPFVLTQDF	LIVISKGAQE	CTKTREFERF	QEMCYKAYLA	IRQHANLFIN
LFSMMLGSGM	PELQSFDDIA	YIRKTLALDK	TEQEALEYFM	KQMNDAHHGG
WTTKMDWIFH	TIKQHALN

Funkcija

Fosfatidilinozitol-4,5-bisfosfat 3-kinaza (takođe zvana fosfatidilinozitol 3-kinaza (PI3K)) se sastoji od 85 kDa regulatorne podjedinice i 110 kDa katalitske podjedinice . Protein kodiran ovim genom predstavlja katalitsku podjedinicu koja koristi ATP za fosforilaciju fosfatidilinozitol (PtdIns), [[fosfatidilinozitol 4-fosfat|PtdIns4P]4] i fosfatidilinozitola i PtdIns(4,5)P2.^[8]

O učešću p110α u ljudskom karcinomu se pretpostavlja od 1995. Potpora za ovu hipotezu došla je iz genetilkih i funkcionalnih studija, uključujući otkriće uobičajenih aktivirajućih misens mutacija PIK3CA u uobičajenim ljudskim tumorima.^[9] Utvrđeno je da je onkogena i da je upletena u rak grlića maternice.^[10] Mutacije PIK3CA prisutne su u više od jedne trećine karcinoma dojke, sa obogaćenjem lumenskih i 2-pozitivnih podtipova receptora epidermnog faktora rasta (HER2+). Tri pozicije mutacije žarišnih tačaka (GLU542, GLU545 i HIS1047) su do danas naširoko prijavljivane.^[11] Dok značajni pretklinički podaci pokazuju povezanost sa snažnom aktivacijom puta i rezistencijom na uobičajene terapije, klinički podaci ne ukazuju da su takve mutacije povezane s visokim razinama aktivacije puta ili s lošom prognozom. Nije poznato da li mutacija predviđa povećanu osjetljivost na agense koji ciljaju P3K put.^[12]

PIK3CA učestvuje u složenoj interakciji unutar tumorskog mikrookruženja u ovom fenomenu.^[13]

Klinički značaj

Zbog povezanosti između p110α i raka,^[14] to može biti odgovarajuća meta lijeka. Farmaceutske kompanije dizajniraju i karakteriziraju potencijalne inhibitore specifične za izoformu p110α.^[15]^[16]

Prisustvo [a] PIK3CA mutacije može predvidjeti odgovor na terapiju aspirinom za kolorektumski karcinom.^[17]^[18]

Somatske aktivirajuće mutacije u PIK3CA nalaze se u poremećajima zvanim Klippel-Trenaunayev sindrom i venska malformacija.^[19]^[20]

PIK3CA vezani segmentni rast uključuje poremećaje mozga kao što su makrocefalija-kapilarna malformacija (MCAP) i hemimegalencefalija. Također je povezan s kongenitalnim, lipomatoznim prekomjernim rastom vaskularnih malformacija, epidermnim nevusima i skeletnim/spinalnim anomalijama (CLOVES sindrom) i fibroadipoznom hiperplazijom (FH). Stanja su uzrokovana heterozigotnim (obično somatskim mozaičnim) mutacijama.^[21]

Inhibicija

Sve PI 3-kinaze inhibiraju lijekovi wortmannin i LY294002, ali wortmannin pokazuje bolju efikasnost od LY294002 na pozicijama žarišta mutacije.^[11]^[22]

Farmakologija

U septembru 2017. Copanlisib, koji inhibira pretežno p110α i p110δ, dobio je FDA odobrenje za liječenje odraslih pacijenata s relapsom folikulskog limfoma (FL) koji su primili najmanje dva prethodne sistemske terapije.^[23]

Interakcije

Pokazalo se da P110α u interakciji sa:

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000121879 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027665 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (august 1992). "Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit". Cell. 70 (3): 419–29. doi:10.1016/0092-8674(92)90166-A. PMID 1322797.
^ Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT (2013). "Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology". Oncogene. 33 (23): 2949–2955. doi:10.1038/onc.2013.244. PMC 3818472. PMID 23792451.
^ "UniProt, P42336" (jezik: engleski). Pristupljeno 9. 11. 2021.
^ "Entrez Gene: PIK3CA".
^ Samuels Y, Waldman T (1. 1. 2010). "Oncogenic mutations of PIK3CA in human cancers". u Rommel C, Vanhaesebroeck B, Vogt PK (ured.). Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology. 347. Springer Berlin Heidelberg. str. 21–41. doi:10.1007/82_2010_68. ISBN 9783642148156. PMC 3164550. PMID 20535651.
^ Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (maj 2000). "PIK3CA as an oncogene in cervical cancer". Oncogene. 19 (23): 2739–44. doi:10.1038/sj.onc.1203597. PMID 10851074.
^ ^a ^b Thirumal Kumar D, George Priya Doss C (septembar 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach". Journal of Biomolecular Structure & Dynamics. 35 (12): 2745–2757. doi:10.1080/07391102.2016.1231082. PMID 27581627.
^ Zardavas D, Phillips WA, Loi S (januar 2014). "PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data". Breast Cancer Research. 16 (1): 201. doi:10.1186/bcr3605. PMC 4054885. PMID 25192370.
^ Fuchs CS, Ogino S (decembar 2013). "Aspirin therapy for colorectal cancer with PIK3CA mutation: simply complex!". Journal of Clinical Oncology. 31 (34): 4358–61. doi:10.1200/jco.2013.52.0080. PMID 24166520.
^ Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kenneth WK, Vogelstein B, Victor Velculescu (april 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science. 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. S2CID 10147415. Greška u vankuverskom stilu: punctuation u nazivu 13 (pomoć)
^ Stein RC (septembar 2001). "Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment". Endocrine-Related Cancer. Bioscientifica. 8 (3): 237–48. doi:10.1677/erc.0.0080237. PMID 11566615.
^ Marone R, Cmiljanovic V, Giese B, Wymann MP (januar 2008). "Targeting phosphoinositide 3-kinase: moving towards therapy". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1784 (1): 159–85. doi:10.1016/j.bbapap.2007.10.003. PMID 17997386.
^ Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (oktobar 2012). "Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival". The New England Journal of Medicine. 367 (17): 1596–606. doi:10.1056/nejmoa1207756. PMC 3532946. PMID 23094721.
^ Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R (decembar 2013). "Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer". Journal of Clinical Oncology. 31 (34): 4297–305. doi:10.1200/jco.2013.50.0322. PMID 24062397.^{[mrtav link]}
^ Limaye N, Kangas J, Mendola A, Godfraind C, Schlögel MJ, Helaers R, Eklund L, Boon LM, Vikkula M (decembar 2015). "Somatic Activating PIK3CA Mutations Cause Venous Malformation". American Journal of Human Genetics. 97 (6): 914–21. doi:10.1016/j.ajhg.2015.11.011. PMC 4678782. PMID 26637981.
^ Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R (april 2015). "Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA". The Journal of Pediatrics. 166 (4): 1048–54.e1–5. doi:10.1016/j.jpeds.2014.12.069. PMC 4498659. PMID 25681199.
^ Mirzaa G, Conway R, Graham JM Jr, Dobyns WB (1. 1. 1993). Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong C, Mefford HC (ured.). "PIK3CA-Related Segmental Overgrowth". University of Washington, Seattle. PMID 23946963. journal zahtijeva |journal= (pomoć)
^ Kumar DT, Doss CG (1. 1. 2016). "Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach". Advances in Protein Chemistry and Structural Biology. 102: 267–97. doi:10.1016/bs.apcsb.2015.09.008. PMID 26827608.
^ "FDA approves new treatment for adults with relapsed follicular lymphoma". US Food and Drug Administration. 14. 9. 2017.
^ Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (august 2003). "Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement". The Journal of Biological Chemistry. 278 (31): 28793–8. doi:10.1074/jbc.M303900200. PMID 12754211.
^ Zemlickova E, Dubois T, Kerai P, Clokie S, Cronshaw AD, Wakefield RI, Johannes FJ, Aitken A (august 2003). "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C". Biochemical and Biophysical Research Communications. 307 (3): 459–65. doi:10.1016/s0006-291x(03)01187-2. PMID 12893243.
^ Luo B, Prescott SM, Topham MK (oktobar 2003). "Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta". The Journal of Biological Chemistry. 278 (41): 39542–7. doi:10.1074/jbc.M307153200. PMID 12890670.
^ Vargiu P, De Abajo R, Garcia-Ranea JA, Valencia A, Santisteban P, Crespo P, Bernal J (januar 2004). "The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors". Oncogene. 23 (2): 559–68. doi:10.1038/sj.onc.1207161. PMID 14724584.
^ Li W, Han M, Guan KL (april 2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf". Genes & Development. 14 (8): 895–900. PMC 316541. PMID 10783161.
^ Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J (maj 1996). "Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation". The EMBO Journal. 15 (10): 2442–51. doi:10.1002/j.1460-2075.1996.tb00602.x. PMC 450176. PMID 8665852.
^ Sade H, Krishna S, Sarin A (januar 2004). "The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells". The Journal of Biological Chemistry. 279 (4): 2937–44. doi:10.1074/jbc.M309924200. PMID 14583609.
^ Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE (decembar 1993). "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". Molecular and Cellular Biology. 13 (12): 7708–17. doi:10.1128/mcb.13.12.7708. PMC 364842. PMID 8246987.

Dopunska literatura

Foster FM, Traer CJ, Abraham SM, Fry MJ (august 2003). "The phosphoinositide (PI) 3-kinase family". Journal of Cell Science. 116 (Pt 15): 3037–40. doi:10.1242/jcs.00609. PMID 12829733.
Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, So S, Chen X, Yuen ST, Leung SY (mart 2005). "Mutations of PIK3CA in gastric adenocarcinoma". BMC Cancer. 5: 29. doi:10.1186/1471-2407-5-29. PMC 1079799. PMID 15784156.
Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW, Vogelstein B, Gabelli SB, Amzel LM (decembar 2007). "The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations". Science. 318 (5857): 1744–8. Bibcode:2007Sci...318.1744H. doi:10.1126/science.1150799. PMID 18079394. S2CID 83474940.
Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW, Liu B, Dawson SJ, Abraham J, Northen H, Peden JF, Mukherjee A, Turashvili G, Green AR, McKinney S, Oloumi A, Shah S, Rosenfeld N, Murphy L, Bentley DR, Ellis IO, Purushotham A, Pinder SE, Børresen-Dale AL, Earl HM, Pharoah PD, Ross MT, Aparicio S, Caldas C (maj 2016). "The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes". Nature Communications. 7: 11479. Bibcode:2016NatCo...711479P. doi:10.1038/ncomms11479. PMC 4866047. PMID 27161491.

Vanjski linkovi

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000121879 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027665 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1322797-5] Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (august 1992). "Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit". Cell. 70 (3): 419–29. doi:10.1016/0092-8674(92)90166-A. PMID 1322797.

[6] Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT (2013). "Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology". Oncogene. 33 (23): 2949–2955. doi:10.1038/onc.2013.244. PMC 3818472. PMID 23792451.

[UniProt-7] "UniProt, P42336" (jezik: engleski). Pristupljeno 9. 11. 2021.

[entrez-8] "Entrez Gene: PIK3CA".

[9] Samuels Y, Waldman T (1. 1. 2010). "Oncogenic mutations of PIK3CA in human cancers". u Rommel C, Vanhaesebroeck B, Vogt PK (ured.). Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology. 347. Springer Berlin Heidelberg. str. 21–41. doi:10.1007/82_2010_68. ISBN 9783642148156. PMC 3164550. PMID 20535651.

[pmid10851074-10] Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (maj 2000). "PIK3CA as an oncogene in cervical cancer". Oncogene. 19 (23): 2739–44. doi:10.1038/sj.onc.1203597. PMID 10851074.

[Role_of_E542_and_E545_missense_muta-11] Thirumal Kumar D, George Priya Doss C (septembar 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach". Journal of Biomolecular Structure & Dynamics. 35 (12): 2745–2757. doi:10.1080/07391102.2016.1231082. PMID 27581627.

[12] Zardavas D, Phillips WA, Loi S (januar 2014). "PIK3CA mutations in breast cancer: reconciling findings from preclinical and clinical data". Breast Cancer Research. 16 (1): 201. doi:10.1186/bcr3605. PMC 4054885. PMID 25192370.

[13] Fuchs CS, Ogino S (decembar 2013). "Aspirin therapy for colorectal cancer with PIK3CA mutation: simply complex!". Journal of Clinical Oncology. 31 (34): 4358–61. doi:10.1200/jco.2013.52.0080. PMID 24166520.

[pmid15016963-14] Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kenneth WK, Vogelstein B, Victor Velculescu (april 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science. 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. S2CID 10147415. Greška u vankuverskom stilu: punctuation u nazivu 13 (pomoć)

[pmid11566615-15] Stein RC (septembar 2001). "Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment". Endocrine-Related Cancer. Bioscientifica. 8 (3): 237–48. doi:10.1677/erc.0.0080237. PMID 11566615.

[pmid17997386-16] Marone R, Cmiljanovic V, Giese B, Wymann MP (januar 2008). "Targeting phosphoinositide 3-kinase: moving towards therapy". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1784 (1): 159–85. doi:10.1016/j.bbapap.2007.10.003. PMID 17997386.

[17] Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (oktobar 2012). "Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival". The New England Journal of Medicine. 367 (17): 1596–606. doi:10.1056/nejmoa1207756. PMC 3532946. PMID 23094721.

[18] Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R (decembar 2013). "Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer". Journal of Clinical Oncology. 31 (34): 4297–305. doi:10.1200/jco.2013.50.0322. PMID 24062397.^{[mrtav link]}

[19] Limaye N, Kangas J, Mendola A, Godfraind C, Schlögel MJ, Helaers R, Eklund L, Boon LM, Vikkula M (decembar 2015). "Somatic Activating PIK3CA Mutations Cause Venous Malformation". American Journal of Human Genetics. 97 (6): 914–21. doi:10.1016/j.ajhg.2015.11.011. PMC 4678782. PMID 26637981.

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