KEGG   PATHWAY: pvp05224
Entry
pvp05224                    Pathway                                
Name
Breast cancer - Pteropus vampyrus (large flying fox)
Description
Breast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. In the case of breast cancer only 8% of all cancers are hereditary, a phenomenon linked to genetic changes in BRCA1 or BRCA2. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers.
Class
Human Diseases; Cancer: specific types
Pathway map
pvp05224  Breast cancer
pvp05224

Disease
H00031  Breast cancer
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288383  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105288649  DLL4; delta-like protein 4 isoform X2 [KO:K06051]
105288737  FGF7; fibroblast growth factor 7 [KO:K04358]
105288811  SHC4; SHC-transforming protein 4 [KO:K17449]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289767  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
105290030  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
105290156  WNT16; protein Wnt-16 [KO:K01558]
105290270  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
105290328  CTNNB1; catenin beta-1 [KO:K02105]
105290434  WNT4; protein Wnt-4 [KO:K00408]
105290449  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105291051  WNT10A; protein Wnt-10a [KO:K01357]
105291052  WNT6; protein Wnt-6 isoform X2 [KO:K00445]
105291153  HEY2; hairy/enhancer-of-split related with YRPW motif protein 2 [KO:K09091]
105291226  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105291480  TCF7L2; transcription factor 7-like 2 isoform X8 [KO:K04491]
105291512  FZD3; frizzled-3 isoform X1 [KO:K02329]
105291659  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
105291733  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
105292122  FGF9; fibroblast growth factor 9 [KO:K04358]
105292386  FGF5; fibroblast growth factor 5 [KO:K04358]
105292561  MYC; myc proto-oncogene protein [KO:K04377]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293004  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105293045  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105293112  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105293259  FGF6; fibroblast growth factor 6 [KO:K04358]
105293279  FGF23; fibroblast growth factor 23 [KO:K22428]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293567  TCF7; transcription factor 7 isoform X2 [KO:K02620]
105293607  WNT8A; protein Wnt-8a [KO:K00714]
105293773  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
105293851  ESR1; estrogen receptor [KO:K08550]
105293923  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294187  FZD4; frizzled-4 [KO:K02354]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294446  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
105294552  FZD1; frizzled-1 [KO:K02432]
105294978  WNT7A; protein Wnt-7a [KO:K00572]
105295478  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
105295548  FGF20; fibroblast growth factor 20 [KO:K04358]
105295887  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105296379  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
105296547  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296814  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
105297044  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
105297140  [KO:K02649]
105297256  WNT5B; protein Wnt-5b isoform X1 [KO:K00444]
105297527  WNT10B; protein Wnt-10b [KO:K01357]
105297529  WNT1; proto-oncogene Wnt-1 [KO:K03209]
105297627  WNT11; protein Wnt-11 [KO:K01384]
105297749  AXIN2; axin-2 [KO:K04385]
105297815  NOTCH2; neurogenic locus notch homolog protein 2 [KO:K20994]
105298116  FZD7; frizzled-7 [KO:K02432]
105298182  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
105298271  PGR; progesterone receptor [KO:K08556]
105298400  FZD5; frizzled-5 [KO:K02375]
105298465  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
105298541  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
105298625  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298799  JAG1; protein jagged-1 isoform X1 [KO:K06052]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299213  FOS; proto-oncogene c-Fos [KO:K04379]
105299317  FGF18; fibroblast growth factor 18 [KO:K04358]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299427  CSNK1A1; casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
105299568  FZD10; frizzled-10 [KO:K02842]
105299684  FZD9; frizzled-9 [KO:K02842]
105299863  WNT5A; protein Wnt-5a isoform X5 [KO:K00444]
105299958  WNT3A; protein Wnt-3a [KO:K00312]
105300002  WNT9A; protein Wnt-9a [KO:K01064]
105300011  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
105300023  RB1; retinoblastoma-associated protein [KO:K06618]
105300159  [KO:K04456] [EC:2.7.11.1]
105300221  DLL3; delta-like protein 3 [KO:K06051]
105300252  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105300265  SHC3; SHC-transforming protein 3 [KO:K17448]
105300315  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105300424  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105300873  FZD6; frizzled-6 isoform X1 [KO:K02376]
105301000  [KO:K14021]
105301286  FGF10; fibroblast growth factor 10 [KO:K04358]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301374  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
105301762  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
105301799  FGF21; fibroblast growth factor 21 [KO:K22429]
105302044  WNT7B; protein Wnt-7b [KO:K00572]
105302100  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
105302177  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
105302250  FGF22; fibroblast growth factor 22 [KO:K04358]
105302259  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
105302278  SHC2; SHC-transforming protein 2 [KO:K17447]
105302449  BRCA2; LOW QUALITY PROTEIN: breast cancer type 2 susceptibility protein [KO:K08775]
105302655  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
105302799  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
105302953  HEY1; hairy/enhancer-of-split related with YRPW motif protein 1 isoform X1 [KO:K09091]
105303252  AXIN1; axin-1 isoform X1 [KO:K02157]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105303453  WNT3; proto-oncogene Wnt-3 [KO:K00312]
105303454  WNT9B; protein Wnt-9b [KO:K01064]
105303480  FZD2; frizzled-2 [KO:K02235]
105303599  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
105303719  DLL1; delta-like protein 1 isoform X3 [KO:K06051]
105303895  JAG2; protein jagged-2 [KO:K21635]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304277  E2F1; transcription factor E2F1 [KO:K17454]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105304647  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
105304667  WNT8B; protein Wnt-8b [KO:K00714]
105305275  NOTCH4; neurogenic locus notch homolog protein 4 isoform X3 [KO:K20996]
105305459  ARAF; serine/threonine-protein kinase A-Raf isoform X8 [KO:K08845] [EC:2.7.11.1]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306141  [KO:K04361] [EC:2.7.10.1]
105306256  BRCA1; breast cancer type 1 susceptibility protein isoform X1 [KO:K10605] [EC:2.3.2.27]
105306395  HES1; transcription factor HES-1 [KO:K06054]
105306550  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
105306578  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105307123  [KO:K22603]
105307126  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
105307127  [KO:K22603]
105307128  [KO:K04503]
105307149  FZD8; frizzled-8 [KO:K02375]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307393  CDK4; cyclin-dependent kinase 4 isoform X2 [KO:K02089] [EC:2.7.11.22]
105307498  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105308251  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
105308466  WNT2; protein Wnt-2 [KO:K00182]
105308555  ESR2; estrogen receptor beta isoform X2 [KO:K08551]
105308889  FGF16; fibroblast growth factor 16 [KO:K04358]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309663  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
105309743  HEYL; hairy/enhancer-of-split related with YRPW motif-like protein [KO:K09091]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105309888  [KO:K04358]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
105311363  FGF4; fibroblast growth factor 4 [KO:K04358]
111728746  [KO:K14021]
Compound
C00410  Progesterone
C00951  Estradiol-17beta
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:24649067
  Authors
Zhang MH, Man HT, Zhao XD, Dong N, Ma SL
  Title
Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review).
  Journal
Biomed Rep 2:41-52 (2014)
DOI:10.3892/br.2013.187
Reference
PMID:27390604
  Authors
Dai X, Xiang L, Li T, Bai Z
  Title
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
  Journal
J Cancer 7:1281-94 (2016)
DOI:10.7150/jca.13141
Reference
PMID:20436504
  Authors
Schnitt SJ
  Title
Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy.
  Journal
Mod Pathol 23 Suppl 2:S60-4 (2010)
DOI:10.1038/modpathol.2010.33
Reference
PMID:23000897
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  Title
Comprehensive molecular portraits of human breast tumours.
  Journal
Nature 490:61-70 (2012)
DOI:10.1038/nature11412
Reference
PMID:22178455
  Authors
Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A
  Title
Molecular biology in breast cancer: intrinsic subtypes and signaling pathways.
  Journal
Cancer Treat Rev 38:698-707 (2012)
DOI:10.1016/j.ctrv.2011.11.005
Reference
  Authors
Karamouzis MV, Papavassiliou KA, Adamopoulos C, Papavassiliou AG.
  Title
Targeting androgen/estrogen receptors crosstalk in cancer
  Journal
Trends Cancer 2:35-48 (2016)
DOI:10.1016/j.trecan.2015.12.001
Reference
  Authors
Sharp A, Harper-Wynne C.
  Title
Treatment of advanced breast cancer (ABC): the expanding landscape of targeted therapies
  Journal
J Cancer Biol Res 2:1036 (2014)
Reference
PMID:24596345
  Authors
Byler S, Goldgar S, Heerboth S, Leary M, Housman G, Moulton K, Sarkar S
  Title
Genetic and epigenetic aspects of breast cancer progression and therapy.
  Journal
Anticancer Res 34:1071-7 (2014)
Reference
PMID:23988612
  Authors
Mohamed A, Krajewski K, Cakar B, Ma CX
  Title
Targeted therapy for breast cancer.
  Journal
Am J Pathol 183:1096-112 (2013)
DOI:10.1016/j.ajpath.2013.07.005
Reference
PMID:22722193
  Authors
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LL, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER
  Title
Whole-genome analysis informs breast cancer response to aromatase inhibition.
  Journal
Nature 486:353-60 (2012)
DOI:10.1038/nature11143
Reference
PMID:25907219
  Authors
Ma CX, Reinert T, Chmielewska I, Ellis MJ
  Title
Mechanisms of aromatase inhibitor resistance.
  Journal
Nat Rev Cancer 15:261-75 (2015)
DOI:10.1038/nrc3920
Reference
PMID:16113099
  Authors
Butt AJ, McNeil CM, Musgrove EA, Sutherland RL
  Title
Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E.
  Journal
Endocr Relat Cancer 12 Suppl 1:S47-59 (2005)
DOI:10.1677/erc.1.00993
Reference
PMID:24111892
  Authors
Dasgupta S, Lonard DM, O'Malley BW
  Title
Nuclear receptor coactivators: master regulators of human health and disease.
  Journal
Annu Rev Med 65:279-92 (2014)
DOI:10.1146/annurev-med-051812-145316
Reference
PMID:23702927
  Authors
Brisken C
  Title
Progesterone signalling in breast cancer: a neglected hormone coming into the limelight.
  Journal
Nat Rev Cancer 13:385-96 (2013)
DOI:10.1038/nrc3518
Reference
PMID:20087430
  Authors
Scarpin KM, Graham JD, Mote PA, Clarke CL
  Title
Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression.
  Journal
Nucl Recept Signal 7:e009 (2009)
DOI:10.1621/nrs.07009
Reference
PMID:24291072
  Authors
Knutson TP, Lange CA
  Title
Tracking progesterone receptor-mediated actions in breast cancer.
  Journal
Pharmacol Ther 142:114-25 (2014)
DOI:10.1016/j.pharmthera.2013.11.010
Reference
PMID:25544707
  Authors
Dittrich A, Gautrey H, Browell D, Tyson-Capper A
  Title
The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.
  Journal
J Mammary Gland Biol Neoplasia 19:253-70 (2014)
DOI:10.1007/s10911-014-9329-5
Reference
PMID:21965336
  Authors
Higgins MJ, Baselga J
  Title
Targeted therapies for breast cancer.
  Journal
J Clin Invest 121:3797-803 (2011)
DOI:10.1172/JCI57152
Reference
PMID:26028978
  Authors
Mukohara T
  Title
PI3K mutations in breast cancer: prognostic and therapeutic implications.
  Journal
Breast Cancer (Dove Med Press) 7:111-23 (2015)
DOI:10.2147/BCTT.S60696
Reference
PMID:19088017
  Authors
Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA
  Title
Triple-negative breast cancer: risk factors to potential targets.
  Journal
Clin Cancer Res 14:8010-8 (2008)
DOI:10.1158/1078-0432.CCR-08-1208
Reference
PMID:21898546
  Authors
King TD, Suto MJ, Li Y
  Title
The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer.
  Journal
J Cell Biochem 113:13-8 (2012)
DOI:10.1002/jcb.23350
Reference
PMID:11737884
  Authors
Brown AM
  Title
Wnt signaling in breast cancer: have we come full circle?
  Journal
Breast Cancer Res 3:351-5 (2001)
DOI:10.1186/bcr321
Reference
PMID:21076461
  Authors
Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, Natrajan R, Reis-Filho JS
  Title
beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation.
  Journal
Mod Pathol 24:209-31 (2011)
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Reference
PMID:20971825
  Authors
Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS
  Title
Notch signaling pathway as a therapeutic target in breast cancer.
  Journal
Mol Cancer Ther 10:9-15 (2011)
DOI:10.1158/1535-7163.MCT-10-0677
Reference
PMID:26968398
  Authors
Rangel MC, Bertolette D, Castro NP, Klauzinska M, Cuttitta F, Salomon DS
  Title
Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer.
  Journal
Breast Cancer Res Treat 156:211-26 (2016)
DOI:10.1007/s10549-016-3746-7
Reference
PMID:26040571
  Authors
Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N
  Title
Therapeutic targets of triple-negative breast cancer: a review.
  Journal
Br J Pharmacol 172:4228-37 (2015)
DOI:10.1111/bph.13211
Reference
PMID:23196196
  Authors
Karamboulas C, Ailles L
  Title
Developmental signaling pathways in cancer stem cells of solid tumors.
  Journal
Biochim Biophys Acta 1830:2481-95 (2013)
DOI:10.1016/j.bbagen.2012.11.008
Reference
PMID:23881035
  Authors
Ignatiadis M, Sotiriou C
  Title
Luminal breast cancer: from biology to treatment.
  Journal
Nat Rev Clin Oncol 10:494-506 (2013)
DOI:10.1038/nrclinonc.2013.124
Reference
PMID:25013431
  Authors
Shin SJ, Gong G, Lee HJ, Kang J, Bae YK, Lee A, Cho EY, Lee JS, Suh KS, Lee DW, Jung WH
  Title
Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status and a favorable prognosis in breast cancer.
  Journal
J Breast Cancer 17:113-20 (2014)
DOI:10.4048/jbc.2014.17.2.113
Reference
PMID:11879567
  Authors
Gasco M, Shami S, Crook T
  Title
The p53 pathway in breast cancer.
  Journal
Breast Cancer Res 4:70-6 (2002)
DOI:10.1186/bcr426
Reference
PMID:15343273
  Authors
Narod SA, Foulkes WD
  Title
BRCA1 and BRCA2: 1994 and beyond.
  Journal
Nat Rev Cancer 4:665-76 (2004)
DOI:10.1038/nrc1431
Related
pathway
pvp03440  Homologous recombination
pvp04010  MAPK signaling pathway
pvp04110  Cell cycle
pvp04115  p53 signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04310  Wnt signaling pathway
pvp04330  Notch signaling pathway
pvp04915  Estrogen signaling pathway
KO pathway
ko05224   

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