KEGG   PATHWAY: tup05224
Entry
tup05224                    Pathway                                
Name
Breast cancer - Tupaia chinensis (Chinese tree shrew)
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
tup05224  Breast cancer
tup05224

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102497715  ESR1; estrogen receptor 1 [KO:K08550]
102492213  ESR2; estrogen receptor 2 [KO:K08551]
102476171  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
102496469  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
102491199  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102496870  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102473003  SP1; Sp1 transcription factor [KO:K04684]
102490651  CCND1; cyclin D1 [KO:K04503]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102503083  PGR; progesterone receptor [KO:K08556]
102499190  WNT1; Wnt family member 1 [KO:K03209]
102493340  WNT4; Wnt family member 4 [KO:K00408]
102487682  TNFSF11; tumor necrosis factor superfamily member 11 [KO:K05473]
102487164  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
102472932  FGF1; fibroblast growth factor 1 [KO:K18496]
102498637  FGF2; fibroblast growth factor 2 [KO:K18497]
102489294  FGF9; fibroblast growth factor 9 [KO:K04358]
102500824  FGF16; fibroblast growth factor 16 [KO:K04358]
102496950  FGF18; fibroblast growth factor 18 [KO:K04358]
102470973  FGF20; fibroblast growth factor 20 [KO:K04358]
102477924  FGF17; fibroblast growth factor 17 [KO:K04358]
102492980  FGF5; fibroblast growth factor 5 [KO:K04358]
102478652  FGF6; fibroblast growth factor 6 [KO:K04358]
102470048  FGF3; fibroblast growth factor 3 [KO:K04358]
102470471  FGF4; fibroblast growth factor 4 [KO:K04358]
102496545  FGF8; fibroblast growth factor 8 [KO:K04358]
102500031  FGF10; fibroblast growth factor 10 [KO:K04358]
102494532  FGF22; fibroblast growth factor 22 [KO:K04358]
102476072  FGF7; fibroblast growth factor 7 [KO:K04358]
102470889  FGF19; fibroblast growth factor 19 [KO:K22603]
102480823  fibroblast growth factor 19-like [KO:K22603]
102474175  FGF21; fibroblast growth factor 21 [KO:K22429]
102479073  FGF23; fibroblast growth factor 23 [KO:K22428]
102484087  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
102490248  IGF1; insulin like growth factor 1 [KO:K05459]
102473496  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102490423  EGF; epidermal growth factor [KO:K04357]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102489301  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
102481002  SHC1; SHC adaptor protein 1 [KO:K06279]
102481863  SHC2; SHC adaptor protein 2 [KO:K17447]
102472295  SHC3; SHC adaptor protein 3 [KO:K17448]
102479734  SHC4; SHC adaptor protein 4 [KO:K17449]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102494629  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102477222  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102493239  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102477389  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106736453  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102489114  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102485262  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102493152  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
102475423  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
102476608  JAG1; jagged 1 [KO:K06052]
102471501  JAG2; jagged 2 [KO:K21635]
102479901  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
102468123  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
102480910  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
102482344  NOTCH1; notch 1 [KO:K02599]
102479715  NOTCH2; notch 2 [KO:K20994]
102471365  NOTCH3; notch 3 [KO:K20995]
102493414  NOTCH4; notch 4 [KO:K20996]
102495758  HES1; hes family bHLH transcription factor 1 [KO:K06054]
102498706  HES5; hes family bHLH transcription factor 5 [KO:K06055]
102469503  HEY2; hes related family bHLH transcription factor with YRPW motif 2 [KO:K09091]
102484242  HEYL; hes related family bHLH transcription factor with YRPW motif-like [KO:K09091]
102473000  HEY1; hes related family bHLH transcription factor with YRPW motif 1 [KO:K09091]
102482918  FLT4; fms related tyrosine kinase 4 [KO:K05097] [EC:2.7.10.1]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102497537  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
102479831  WNT2B; Wnt family member 2B [KO:K00182]
102483867  WNT2; Wnt family member 2 [KO:K00182]
102501628  WNT3A; Wnt family member 3A [KO:K00312]
102489001  WNT3; Wnt family member 3 [KO:K00312]
102489573  WNT5A; Wnt family member 5A [KO:K00444]
102467720  WNT5B; Wnt family member 5B [KO:K00444]
102483667  WNT6; Wnt family member 6 [KO:K00445]
102484353  WNT7A; Wnt family member 7A [KO:K00572]
102500004  WNT7B; Wnt family member 7B [KO:K00572]
102468229  WNT8B; Wnt family member 8B [KO:K00714]
102490209  WNT8A; Wnt family member 8A [KO:K00714]
102496226  WNT9A; Wnt family member 9A [KO:K01064]
102489417  WNT9B; Wnt family member 9B [KO:K01064]
102481567  WNT10B; Wnt family member 10B [KO:K01357]
102483253  WNT10A; Wnt family member 10A [KO:K01357]
102494826  WNT11; Wnt family member 11 [KO:K01384]
102497530  WNT16; Wnt family member 16 [KO:K01558]
102492163  FZD7; frizzled class receptor 7 [KO:K02432]
102499195  FZD1; frizzled class receptor 1 [KO:K02432]
102479307  FZD2; frizzled class receptor 2 [KO:K02235]
102474963  FZD3; frizzled class receptor 3 [KO:K02329]
102491949  FZD4; frizzled class receptor 4 [KO:K02354]
102475157  FZD5; frizzled class receptor 5 [KO:K02375]
102487480  FZD8; frizzled class receptor 8 [KO:K02375]
102492375  FZD6; frizzled class receptor 6 [KO:K02376]
102479813  FZD10; frizzled class receptor 10 [KO:K02842]
102481011  FZD9; frizzled class receptor 9 [KO:K02842]
102502071  LRP6; LDL receptor related protein 6 [KO:K03068]
102473447  LRP5L; LDL receptor related protein 5 like [KO:K03068]
102485749  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
102472352  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
102468994  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
102476038  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102469399  AXIN1; axin 1 [KO:K02157]
102493766  AXIN2; axin 2 [KO:K04385]
102484859  APC; APC, WNT signaling pathway regulator [KO:K02085]
102470052  APC2; APC2, WNT signaling pathway regulator [KO:K02085]
102472740  CTNNB1; catenin beta 1 [KO:K02105]
102487962  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
102484318  TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
102481394  TCF7L1; transcription factor 7 like 1 [KO:K04490]
102472810  TCF7L2; transcription factor 7 like 2 [KO:K04491]
102474621  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
102503238  TP53; tumor protein p53 [KO:K04451]
102496861  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102476523  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102502813  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102471776  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102476690  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102472614  DDB2; damage specific DNA binding protein 2 [KO:K10140]
102479454  POLK; DNA polymerase kappa [KO:K03511] [EC:2.7.7.7]
102493291  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102488432  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102499507  RB1; RB transcriptional corepressor 1 [KO:K06618]
102484832  E2F1; E2F transcription factor 1 [KO:K17454]
102479669  E2F2; E2F transcription factor 2 [KO:K09389]
102499416  E2F3; E2F transcription factor 3 [KO:K06620]
102494934  BRCA1; BRCA1, DNA repair associated [KO:K10605] [EC:2.3.2.27]
102491921  BRCA2; BRCA2, DNA repair associated [KO:K08775]
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
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Dai X, Xiang L, Li T, Bai Z
  Title
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
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J Cancer 7:1281-94 (2016)
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Reference
PMID:20436504
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Schnitt SJ
  Title
Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy.
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Mod Pathol 23 Suppl 2:S60-4 (2010)
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Reference
PMID:23000897
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Comprehensive molecular portraits of human breast tumours.
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Nature 490:61-70 (2012)
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Reference
PMID:22178455
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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
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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
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Sharp A, Harper-Wynne C.
  Title
Treatment of advanced breast cancer (ABC): the expanding landscape of targeted therapies
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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.
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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)
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Reference
PMID:16113099
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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.
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Endocr Relat Cancer 12 Suppl 1:S47-59 (2005)
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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
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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)
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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
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  Title
Notch signaling pathway as a therapeutic target in breast cancer.
  Journal
Mol Cancer Ther 10:9-15 (2011)
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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
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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
tup03440  Homologous recombination
tup04010  MAPK signaling pathway
tup04110  Cell cycle
tup04115  p53 signaling pathway
tup04151  PI3K-Akt signaling pathway
tup04310  Wnt signaling pathway
tup04330  Notch signaling pathway
tup04915  Estrogen signaling pathway
KO pathway
ko05224   
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