KEGG   PATHWAY: pale05224
Entry
pale05224                   Pathway                                
Name
Breast cancer - Pteropus alecto (black 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
pale05224  Breast cancer
pale05224

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102877910  ESR1; estrogen receptor isoform X1 [KO:K08550]
102878324  ESR2; estrogen receptor beta isoform X2 [KO:K08551]
102885576  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
102892705  NCOA3; nuclear receptor coactivator 3 isoform X1 [KO:K11256] [EC:2.3.1.48]
102891428  FOS; proto-oncogene c-Fos [KO:K04379]
102896121  JUN; transcription factor AP-1 [KO:K04448]
102894100  SP1; transcription factor Sp1 isoform X1 [KO:K04684]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102895524  MYC; myc proto-oncogene protein [KO:K04377]
102882873  PGR; progesterone receptor isoform X1 [KO:K08556]
102888016  WNT1; proto-oncogene Wnt-1 [KO:K03209]
102888866  WNT4; protein Wnt-4 [KO:K00408]
102896284  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
102885300  ERBB2; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102894192  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
107196088  FGF2; fibroblast growth factor 2 [KO:K18497]
102895922  FGF10; fibroblast growth factor 10 [KO:K04358]
102887777  FGF7; fibroblast growth factor 7 [KO:K04358]
102892141  FGF6; fibroblast growth factor 6 [KO:K04358]
102895642  FGF5; fibroblast growth factor 5 [KO:K04358]
102890153  FGF16; fibroblast growth factor 16 [KO:K04358]
102893226  FGF8; fibroblast growth factor 8 isoform X4 [KO:K04358]
102894115  FGF18; fibroblast growth factor 18 [KO:K04358]
102888098  FGF20; fibroblast growth factor 20 [KO:K04358]
102893244  FGF4; fibroblast growth factor 4 [KO:K04358]
102894279  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
102887882  FGF9; fibroblast growth factor 9 [KO:K04358]
102896895  FGF22; fibroblast growth factor 22 [KO:K04358]
102885081  FGF19; fibroblast growth factor 19 [KO:K22603]
102886540  FGF21; fibroblast growth factor 21 [KO:K22429]
102883346  FGF23; fibroblast growth factor 23 [KO:K22428]
102898943  FGFR1; fibroblast growth factor receptor 1 isoform X9 [KO:K04362] [EC:2.7.10.1]
102890331  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102885962  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102891552  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102895969  KIT; mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
102894443  SHC1; LOW QUALITY PROTEIN: SHC-transforming protein 1 [KO:K06279]
102885958  SHC2; SHC-transforming protein 2 [KO:K17447]
102879956  SHC3; SHC-transforming protein 3 [KO:K17448]
102888926  SHC4; SHC-transforming protein 4 [KO:K17449]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102877877  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
102878393  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102881949  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102885092  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102891214  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102889369  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102883084  JAG1; protein jagged-1 [KO:K06052]
102891267  JAG2; protein jagged-2 [KO:K21635]
102891557  DLL4; delta-like protein 4 isoform X2 [KO:K06051]
102882856  DLL3; delta-like protein 3 [KO:K06051]
102892930  DLL1; delta-like protein 1 [KO:K06051]
102889752  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
102887446  NOTCH2; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 2 [KO:K20994]
102898799  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
102895453  NOTCH4; neurogenic locus notch homolog protein 4 [KO:K20996]
102890128  HES1; transcription factor HES-1 [KO:K06054]
102893116  HES5; transcription factor HES-5 [KO:K06055]
102893208  hairy/enhancer-of-split related with YRPW motif protein 1 [KO:K09091]
102891586  HEY2; hairy/enhancer-of-split related with YRPW motif protein 2 [KO:K09091]
102895448  HEYL; hairy/enhancer-of-split related with YRPW motif-like protein [KO:K09091]
102889771  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102894780  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
102880959  WNT2B; protein Wnt-2b isoform X1 [KO:K00182]
102885080  WNT2; protein Wnt-2 [KO:K00182]
102895795  WNT3A; protein Wnt-3a [KO:K00312]
102877979  WNT3; proto-oncogene Wnt-3 [KO:K00312]
102890342  WNT5A; protein Wnt-5a isoform X5 [KO:K00444]
102881682  WNT5B; protein Wnt-5b isoform X2 [KO:K00444]
102882368  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
102888597  WNT7A; protein Wnt-7a [KO:K00572]
102898026  WNT7B; protein Wnt-7b isoform X1 [KO:K00572]
102896480  WNT8A; protein Wnt-8a [KO:K00714]
102878209  WNT8B; protein Wnt-8b [KO:K00714]
102885223  protein Wnt-9b [KO:K01064]
102884543  WNT9A; protein Wnt-9a [KO:K01064]
102882121  WNT10A; protein Wnt-10a [KO:K01357]
102888263  WNT10B; protein Wnt-10b [KO:K01357]
102877879  WNT11; protein Wnt-11 [KO:K01384]
102882050  WNT16; LOW QUALITY PROTEIN: protein Wnt-16 [KO:K01558]
102880538  FZD7; frizzled-7 [KO:K02432]
102895634  FZD1; frizzled-1 [KO:K02432]
102884150  FZD2; frizzled-2 [KO:K02235]
102890038  FZD3; frizzled-3 isoform X1 [KO:K02329]
102892989  FZD4; LOW QUALITY PROTEIN: frizzled-4 [KO:K02354]
102877864  FZD8; LOW QUALITY PROTEIN: frizzled-8 [KO:K02375]
102883426  FZD5; LOW QUALITY PROTEIN: frizzled-5 [KO:K02375]
102890002  FZD6; frizzled-6 [KO:K02376]
102894135  FZD10; frizzled-10 [KO:K02842]
102878169  FZD9; frizzled-9 [KO:K02842]
102894479  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
102878233  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
102895469  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
102880039  DVL2; segment polarity protein dishevelled homolog DVL-2 isoform X1 [KO:K02353]
102881158  DVL1; segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
102896339  LOW QUALITY PROTEIN: proto-oncogene FRAT1 [KO:K03069]
102882441  GSK3B; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
102878657  AXIN1; axin-1 isoform X1 [KO:K02157]
102885831  AXIN2; axin-2 [KO:K04385]
102880260  APC; adenomatous polyposis coli protein isoform X3 [KO:K02085]
102891886  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
102880017  CTNNB1; LOW QUALITY PROTEIN: catenin beta-1 [KO:K02105]
102884974  CSNK1A1; casein kinase I isoform X3 [KO:K08957] [EC:2.7.11.1]
102885788  TCF7; transcription factor 7 isoform X4 [KO:K02620]
102886093  TCF7L1; transcription factor 7-like 1 [KO:K04490]
102880370  TCF7L2; transcription factor 7-like 2 isoform X2 [KO:K04491]
102886933  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102886440  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102878191  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102885790  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102885135  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
102883540  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
102879479  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
102890888  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102896272  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102895982  BRCA1; breast cancer type 1 susceptibility protein isoform X1 [KO:K10605] [EC:2.3.2.27]
102896802  BRCA2; breast cancer type 2 susceptibility protein [KO:K08775]
Compound
C00410  Progesterone
C00951  Estradiol-17beta
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  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
  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
  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
  Authors
  Title
Comprehensive molecular portraits of human breast tumours.
  Journal
Nature 490:61-70 (2012)
DOI:10.1038/nature11412
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Higgins MJ, Baselga J
  Title
Targeted therapies for breast cancer.
  Journal
J Clin Invest 121:3797-803 (2011)
DOI:10.1172/JCI57152
Reference
  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
  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
  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
  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
  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)
DOI:10.1038/modpathol.2010.205
Reference
  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
  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
  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
  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
  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
  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
  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
  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
pale03440  Homologous recombination
pale04010  MAPK signaling pathway
pale04110  Cell cycle
pale04115  p53 signaling pathway
pale04151  PI3K-Akt signaling pathway
pale04310  Wnt signaling pathway
pale04330  Notch signaling pathway
pale04915  Estrogen signaling pathway
KO pathway
ko05224   
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