KEGG   PATHWAY: gvr05224
Entry
gvr05224                    Pathway                                
Name
Breast cancer - Galeopterus variegatus (Sunda flying lemur)
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
gvr05224  Breast cancer
gvr05224

Disease
H00031  Breast cancer
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103581624  [KO:K02599]
103585001  HEYL; hairy/enhancer-of-split related with YRPW motif-like protein [KO:K09091]
103585172  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103585324  ESR2; estrogen receptor beta [KO:K08551]
103585463  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103585949  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
103586304  FGF5; fibroblast growth factor 5 isoform X1 [KO:K04358]
103586572  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103586698  FZD5; frizzled-5 [KO:K02375]
103586784  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103586841  APC; adenomatous polyposis coli protein isoform X1 [KO:K02085]
103586861  E2F1; transcription factor E2F1 [KO:K17454]
103587215  SHC4; SHC-transforming protein 4 [KO:K17449]
103587751  FGF21; fibroblast growth factor 21 [KO:K22429]
103587762  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103587820  MYC; myc proto-oncogene protein [KO:K04377]
103587883  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103588008  LRP5; low-density lipoprotein receptor-related protein 5 [KO:K03068]
103588100  NFKB2; nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
103588373  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
103588497  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
103588543  DLL4; delta-like protein 4 [KO:K06051]
103588673  FGF7; fibroblast growth factor 7 [KO:K04358]
103588746  FGF20; fibroblast growth factor 20 [KO:K04358]
103588804  WNT8B; protein Wnt-8b [KO:K00714]
103588816  NCOA1; nuclear receptor coactivator 1 isoform X1 [KO:K09101] [EC:2.3.1.48]
103588854  WNT1; proto-oncogene Wnt-1 [KO:K03209]
103588855  WNT10B; protein Wnt-10b [KO:K01357]
103589124  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
103589329  NRAS; GTPase NRas [KO:K07828]
103589434  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103589870  BRCA1; breast cancer type 1 susceptibility protein [KO:K10605] [EC:2.3.2.27]
103589982  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
103590136  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103590234  WNT5B; protein Wnt-5b [KO:K00444]
103590253  E2F3; transcription factor E2F3 [KO:K06620]
103590279  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103590309  FLT4; vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
103590315  FZD4; frizzled-4 [KO:K02354]
103590327  HEY2; hairy/enhancer-of-split related with YRPW motif protein 2 [KO:K09091]
103590450  WNT11; protein Wnt-11 [KO:K01384]
103590618  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
103590624  E2F2; transcription factor E2F2 [KO:K09389]
103590674  WNT7A; protein Wnt-7a [KO:K00572]
103590682  FGF1; fibroblast growth factor 1 isoform X1 [KO:K18496]
103590877  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
103590897  FRAT1; proto-oncogene FRAT1 [KO:K03069]
103590898  FRAT2; GSK-3-binding protein FRAT2 [KO:K03096]
103591400  TP53; cellular tumor antigen p53 [KO:K04451]
103591440  DVL2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
103591744  FGF9; fibroblast growth factor 9 [KO:K04358]
103591759  JAG2; protein jagged-2 [KO:K21635]
103592005  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
103592096  DDB2; DNA damage-binding protein 2 [KO:K10140]
103592163  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
103592192  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103592390  JUN; transcription factor AP-1 [KO:K04448]
103592399  TCF7; transcription factor 7 isoform X1 [KO:K02620]
103592813  SP1; transcription factor Sp1 [KO:K04684]
103592918  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
103593080  JAG1; protein jagged-1 [KO:K06052]
103593431  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
103593663  RB1; retinoblastoma-associated protein [KO:K06618]
103593683  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103593743  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
103593776  WNT2B; protein Wnt-2b [KO:K00182]
103593898  DVL3; segment polarity protein dishevelled homolog DVL-3 isoform X1 [KO:K02353]
103593962  FGF17; fibroblast growth factor 17 [KO:K04358]
103594136  LRP6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
103594183  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
103594351  FGF18; fibroblast growth factor 18 [KO:K04358]
103594788  FZD6; frizzled-6 [KO:K02376]
103594862  DVL1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
103595017  FZD2; frizzled-2 [KO:K02235]
103595208  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
103595295  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103595380  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
103595392  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103595413  FGF8; fibroblast growth factor 8 [KO:K04358]
103595701  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
103595849  BRCA2; breast cancer type 2 susceptibility protein [KO:K08775]
103596055  FZD1; frizzled-1 [KO:K02432]
103596129  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103596180  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
103596384  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103596654  FZD9; frizzled-9 [KO:K02842]
103596735  FZD10; frizzled-10 [KO:K02842]
103597016  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103597068  FGF16; fibroblast growth factor 16 [KO:K04358]
103597115  CSNK1A1; casein kinase I isoform alpha isoform X1 [KO:K08957] [EC:2.7.11.1]
103597215  WNT2; protein Wnt-2 [KO:K00182]
103597246  WNT5A; protein Wnt-5a isoform X1 [KO:K00444]
103597471  AXIN2; axin-2 isoform X1 [KO:K04385]
103597574  WNT3; proto-oncogene Wnt-3 [KO:K00312]
103597576  WNT9B; protein Wnt-9b [KO:K01064]
103597620  FZD7; LOW QUALITY PROTEIN: frizzled-7 [KO:K02432]
103598325  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103598508  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
103598510  DLL3; delta-like protein 3 [KO:K06051]
103598534  [KO:K20994]
103598755  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
103598980  [KO:K00408]
103599501  KRAS; GTPase KRas [KO:K07827]
103599851  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
103600050  HEY1; hairy/enhancer-of-split related with YRPW motif protein 1 isoform X1 [KO:K09091]
103600170  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
103600233  SHC2; SHC-transforming protein 2 [KO:K17447]
103600246  WNT6; protein Wnt-6 isoform X1 [KO:K00445]
103600247  WNT10A; protein Wnt-10a [KO:K01357]
103600324  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103600371  PGR; progesterone receptor [KO:K08556]
103600864  HES1; transcription factor HES-1 [KO:K06054]
103600945  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103601062  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
103601359  DLL1; delta-like protein 1 [KO:K06051]
103601524  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
103602136  FGF10; fibroblast growth factor 10 isoform X1 [KO:K04358]
103603629  NOTCH4; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 4 [KO:K20996]
103603960  FGF23; fibroblast growth factor 23 [KO:K22428]
103604077  FZD3; frizzled-3 [KO:K02329]
103604091  FGF19; fibroblast growth factor 19 [KO:K22603]
103604776  [KO:K04361] [EC:2.7.10.1]
103604797  AXIN1; axin-1 isoform X1 [KO:K02157]
103604998  [KO:K04358]
103604999  FGF3; fibroblast growth factor 3 [KO:K04358]
103605007  WNT16; protein Wnt-16 isoform X1 [KO:K01558]
103605206  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
103605402  WNT8A; protein Wnt-8a [KO:K00714]
103605695  [KO:K00312]
103605697  WNT9A; protein Wnt-9a [KO:K01064]
103605698  [KO:K04456] [EC:2.7.11.1]
103605891  FOS; proto-oncogene c-Fos [KO:K04379]
103607082  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103607313  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
103607489  [KO:K01064]
103608083  SHC3; SHC-transforming protein 3 [KO:K17448]
103608197  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103608454  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103608964  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
103608971  APC2; adenomatous polyposis coli protein 2 [KO:K02085]
103609174  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103609408  FGF6; fibroblast growth factor 6 [KO:K04358]
103609951  WNT7B; protein Wnt-7b [KO:K00572]
103610085  FGF22; fibroblast growth factor 22 [KO:K04358]
103610513  HRAS; GTPase HRas isoform X1 [KO:K02833]
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
gvr03440  Homologous recombination
gvr04010  MAPK signaling pathway
gvr04110  Cell cycle
gvr04115  p53 signaling pathway
gvr04151  PI3K-Akt signaling pathway
gvr04310  Wnt signaling pathway
gvr04330  Notch signaling pathway
gvr04915  Estrogen signaling pathway
KO pathway
ko05224   

DBGET integrated database retrieval system