KEGG   PATHWAY: tmu05224
Entry
tmu05224                    Pathway                                
Name
Breast cancer - Trichechus manatus latirostris (Florida manatee)
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
tmu05224  Breast cancer
tmu05224

Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101351018  estrogen receptor [KO:K08550]
101351029  estrogen receptor beta [KO:K08551]
101348769  nuclear receptor coactivator 1 isoform X2 [KO:K09101] [EC:2.3.1.48]
101346625  nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
101357016  proto-oncogene c-Fos [KO:K04379]
101361653  transcription factor AP-1 [KO:K04448]
101349790  transcription factor Sp1 [KO:K04684]
101359745  G1/S-specific cyclin-D1 [KO:K04503]
101349786  myc proto-oncogene protein [KO:K04377]
101344739  progesterone receptor isoform X1 [KO:K08556]
101352160  proto-oncogene Wnt-1 [KO:K03209]
101361433  LOW QUALITY PROTEIN: protein Wnt-4 [KO:K00408]
101342165  tumor necrosis factor ligand superfamily member 11 [KO:K05473]
101354844  receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
101359380  fibroblast growth factor 1 isoform X1 [KO:K18496]
101342442  LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
101347308  fibroblast growth factor 8 isoform X3 [KO:K04358]
101361747  fibroblast growth factor 18 [KO:K04358]
101360972  fibroblast growth factor 9 [KO:K04358]
101344975  fibroblast growth factor 20 [KO:K04358]
101357665  fibroblast growth factor 7 [KO:K04358]
101348610  fibroblast growth factor 16 [KO:K04358]
101356322  fibroblast growth factor 17 isoform X1 [KO:K04358]
101356591  fibroblast growth factor 10 [KO:K04358]
101353258  fibroblast growth factor 3 [KO:K04358]
101350986  fibroblast growth factor 6 [KO:K04358]
101351769  fibroblast growth factor 22 [KO:K04358]
101347190  fibroblast growth factor 5 isoform X1 [KO:K04358]
101354028  fibroblast growth factor 19 [KO:K22603]
101356236  fibroblast growth factor 21 [KO:K22429]
101351251  fibroblast growth factor 23 [KO:K22428]
101342270  fibroblast growth factor receptor 1 isoform X2 [KO:K04362] [EC:2.7.10.1]
101361934  insulin-like growth factor I isoform X1 [KO:K05459]
101355333  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
101355971  pro-epidermal growth factor [KO:K04357]
101356822  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101357486  mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
101358105  SHC-transforming protein 1 isoform X1 [KO:K06279]
101359726  SHC-transforming protein 2 [KO:K17447]
101360084  SHC-transforming protein 3 [KO:K17448]
101355900  SHC-transforming protein 4 [KO:K17449]
101359012  growth factor receptor-bound protein 2 [KO:K04364]
101359592  son of sevenless homolog 1 isoform X1 [KO:K03099]
101347392  son of sevenless homolog 2 isoform X1 [KO:K03099]
101342804  GTPase HRas isoform X2 [KO:K02833]
101347525  GTPase KRas isoform X3 [KO:K07827]
101344230  GTPase NRas isoform X1 [KO:K07828]
101351589  serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101353421  serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
101357840  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101343332  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101341078  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101355243  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]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101343808  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101343535  ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
101354510  ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101354200  protein jagged-1 [KO:K06052]
101361011  protein jagged-2 [KO:K21635]
101360018  delta-like protein 1 [KO:K06051]
101351506  delta-like protein 4 [KO:K06051]
101361650  delta-like protein 3 [KO:K06051]
101348816  neurogenic locus notch homolog protein 1 [KO:K02599]
101356889  neurogenic locus notch homolog protein 2 isoform X2 [KO:K20994]
101358955  neurogenic locus notch homolog protein 3 [KO:K20995]
101356189  neurogenic locus notch homolog protein 4 isoform X1 [KO:K20996]
101350794  transcription factor HES-1 [KO:K06054]
101348791  transcription factor HES-5 [KO:K06055]
101342441  hairy/enhancer-of-split related with YRPW motif protein 1 isoform X2 [KO:K09091]
101355840  hairy/enhancer-of-split related with YRPW motif-like protein [KO:K09091]
101342863  hairy/enhancer-of-split related with YRPW motif protein 2 [KO:K09091]
101340931  vascular endothelial growth factor receptor 3 [KO:K05097] [EC:2.7.10.1]
101342008  cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101352683  nuclear factor NF-kappa-B p100 subunit isoform X1 [KO:K04469]
101344186  protein Wnt-2 [KO:K00182]
101351340  protein Wnt-2b [KO:K00182]
101345396  protein Wnt-3a [KO:K00312]
101341899  proto-oncogene Wnt-3 [KO:K00312]
101358885  protein Wnt-5a isoform X2 [KO:K00444]
101359902  protein Wnt-5b [KO:K00444]
101341737  LOW QUALITY PROTEIN: protein Wnt-6 [KO:K00445]
101341781  protein Wnt-7a [KO:K00572]
101348949  protein Wnt-7b [KO:K00572]
101342296  protein Wnt-8b [KO:K00714]
101342423  protein Wnt-8a [KO:K00714]
101360002  protein Wnt-9a [KO:K01064]
101342156  protein Wnt-9b [KO:K01064]
101347671  protein Wnt-10a [KO:K01357]
101351717  protein Wnt-10b [KO:K01357]
101340313  protein Wnt-11 [KO:K01384]
101359317  protein Wnt-16 [KO:K01558]
101348994  frizzled-1 [KO:K02432]
101347003  frizzled-7 [KO:K02432]
101347661  frizzled-2 [KO:K02235]
101357820  frizzled-3 [KO:K02329]
101359840  frizzled-4 [KO:K02354]
101361647  frizzled-8 [KO:K02375]
101358150  frizzled-5 [KO:K02375]
101348322  frizzled-6 [KO:K02376]
101356576  frizzled-10 [KO:K02842]
101360249  frizzled-9 [KO:K02842]
101355288  low-density lipoprotein receptor-related protein 5 [KO:K03068]
101358700  low-density lipoprotein receptor-related protein 6 isoform X2 [KO:K03068]
101362049  segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
101360142  segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
101353682  segment polarity protein dishevelled homolog DVL-1 isoform X1 [KO:K02353]
101352077  proto-oncogene FRAT1 [KO:K03069]
101352330  GSK-3-binding protein FRAT2 [KO:K03096]
101349186  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101346985  axin-1 isoform X2 [KO:K02157]
101347495  axin-2 [KO:K04385]
101346660  adenomatous polyposis coli protein 2 [KO:K02085]
101341158  adenomatous polyposis coli protein isoform X1 [KO:K02085]
101351897  catenin beta-1 [KO:K02105]
101341353  casein kinase I isoform X1 [KO:K08957] [EC:2.7.11.1]
101350837  LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
101341696  transcription factor 7-like 1 [KO:K04490]
101345532  transcription factor 7-like 2 isoform X1 [KO:K04491]
101345125  lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
101351852  cellular tumor antigen p53 [KO:K04451]
101353013  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101361119  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101348099  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101356564  apoptosis regulator BAX [KO:K02159]
101341201  bcl-2 homologous antagonist/killer [KO:K14021]
101349998  DNA damage-binding protein 2 [KO:K10140]
101359617  DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
101355276  cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101355952  retinoblastoma-associated protein isoform X3 [KO:K06618]
101357348  transcription factor E2F1 [KO:K17454]
101357556  transcription factor E2F2 [KO:K09389]
101346679  transcription factor E2F3 isoform X1 [KO:K06620]
101356605  breast cancer type 1 susceptibility protein [KO:K10605] [EC:2.3.2.27]
101352659  breast cancer type 2 susceptibility protein [KO:K08775]
111818977  breast cancer type 2 susceptibility protein-like [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
tmu03440  Homologous recombination
tmu04010  MAPK signaling pathway
tmu04110  Cell cycle
tmu04115  p53 signaling pathway
tmu04151  PI3K-Akt signaling pathway
tmu04310  Wnt signaling pathway
tmu04330  Notch signaling pathway
tmu04915  Estrogen signaling pathway
KO pathway
ko05224   
LinkDB

DBGET integrated database retrieval system