Breast cancer pathway (Homo sapiens)

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ScaffoldHereditary breast cancer2LegendNucleusNOTCH1 intracellular cytoplasmic domain translocationActivating mutationUncontrolled proliferationIncreased survivalGenomic instabilityDS breakProliferationSurvivalTranslationProliferationDNA damageRPS6KB1TP53CETN3AngiogenesisFGF6FGF20SKP1FGF18GRB2FGF7HEY1PIP3CDK4Cell cycle (G1/S) progressionFGF5Wnt Signaling PathwayMRE11AEstrogenFGF23BRCA1FGF17Estrogen SignalingPathwayERBB2Cell CycleTCF7p53 SignalingPathwayPTENATMFGF19RAD51FGF21FGF1HES1PARP1FGF16Notch SignalingPathwayProgesteroneFGFR1IGF1RIGF14SHC1SHC2SHC3SHC4SOS1SOS2HRASKRASNRASARAF3BRAFRAF1PIK3CAPIK3CD1PIK3R1PIK3R2PIK3R3AKT1AKT2AKT3MTORRPS6KB2EGFEGFRKITJAG2NOTCH1NOTCH2NOTCH3NOTCH4DLL1DLL3DLL4LRP5LRP6FRAT1FRAT2TCF7L2TCF7L1LEF1MYCCCND1ERBB2FLT4HEY2HEYLHES5CCND1MYCERBB2CDKN1ANFKB2BRCA2Error-prone repair ofdouble-strand breaksChromosomal instabilityCDKN1ABAXDDB2POLKBAK1GADD45GGADD45AGADD45BCDK6RB1PE2F1E2F2E2F3ESR1ESR2PGRESR1ESR2EstrogenPGRProgesteroneESR1ESR2EstrogenPGRProgesteroneNCOA3NCOA1WNT1WNT4TNFSF11NCOA3NCOA1ESR1ESR2EstrogenMYCCCND1CCND1NCOA3NCOA1ESR1ESR2Estradiol-17betaFOSJUNSP1Inactivating mutationFGF2FGF3FGF4FGF8FGF9FGF10FGF22APC2DVL3GSK3BCSNK2BAPCCSNK1A1DVL2CSNK2A1AXIN1DVL1CSNK1A1LCSNK2A3CSNK2A2CTNNB1AXIN2CTNNB1PPP26S Proteasome DegradationFZD3FZD8FZD10FZD7FZD4FZD1FZD6FZD5FZD9FZD2WNT3AWNT7AWNT11WNT1WNT5BWNT2WNT2BWNT6WNT5AWNT16WNT4WNT3WNT10BWNT7BWNT10AWNT16MAP2K1PPMAPK1PPMAPK3PPMAP2K2PPATRRAD50NBN


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:

  • Luminal A subtype: Hormone receptor positive (progesterone and estrogen) and HER2 (ERBB2) negative
  • Luminal B subtype: Hormone receptor positive (progesterone and estrogen) and HER2 (ERBB2) positive
  • HER2 positive: Hormone receptor negative (progesterone and estrogen) and HER2 (ERBB2) positive
  • Basal-like or triple-negative (TNBCs): Hormone receptor negative (progesterone and estrogen) and HER2 (ERBB2) negative

Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumors, 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 signaling 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.

Source: http://www.genome.jp/kegg-bin/show_pathway?hsa05224

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Ontology Terms

 

Bibliography

  1. Mukohara T; ''PI3K mutations in breast cancer: prognostic and therapeutic implications.''; Breast Cancer (Dove Med Press), 2015 PubMed
  2. Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, Wang X, Qiao JW, Cao S, Petralia F, Kawaler E, Mundt F, Krug K, Tu Z, Lei JT, Gatza ML, Wilkerson M, Perou CM, Yellapantula V, Huang KL, Lin C, McLellan MD, Yan P, Davies SR, Townsend RR, Skates SJ, Wang J, Zhang B, Kinsinger CR, Mesri M, Rodriguez H, Ding L, Paulovich AG, Fenyö D, Ellis MJ, Carr SA; ''Proteogenomics connects somatic mutations to signalling in breast cancer.''; Nature, 2016 PubMed
  3. Huang KL, Li S, Mertins P, Cao S, Gunawardena HP, Ruggles KV, Mani DR, Clauser KR, Tanioka M, Usary J, Kavuri SM, Xie L, Yoon C, Qiao JW, Wrobel J, Wyczalkowski MA, Erdmann-Gilmore P, Snider JE, Hoog J, Singh P, Niu B, Guo Z, Sun SQ, Sanati S, Kawaler E, Wang X, Scott A, Ye K, McLellan MD, Wendl MC, Malovannaya A, Held JM, Gillette MA, Fenyö D, Kinsinger CR, Mesri M, Rodriguez H, Davies SR, Perou CM, Ma C, Reid Townsend R, Chen X, Carr SA, Ellis MJ, Ding L; ''Proteogenomic integration reveals therapeutic targets in breast cancer xenografts.''; Nat Commun, 2017 PubMed
  4. Elbauomy Elsheikh S, Green AR, Lambros MB, Turner NC, Grainge MJ, Powe D, Ellis IO, Reis-Filho JS; ''FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis.''; Breast Cancer Res, 2007 PubMed

History

View all...
CompareRevisionActionTimeUserComment
97132view20:27, 30 April 2018Khansperslit refs and connections
97004view23:26, 25 April 2018KhanspersModified title
96965view20:20, 23 April 2018Khansperslayout
96964view19:07, 23 April 2018KhanspersModified description
96937view19:23, 20 April 2018KhanspersOntology Term : 'phosphatidylinositol 3-kinase-Akt signaling pathway' added !
96936view19:23, 20 April 2018KhanspersOntology Term : 'Notch signaling pathway' added !
96925view06:10, 20 April 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
96921view15:57, 19 April 2018KhanspersOntology Term : 'breast cancer pathway' added !
96920view15:57, 19 April 2018KhanspersOntology Term : 'disease pathway' added !
96919view15:56, 19 April 2018KhanspersModified description
96918view15:55, 19 April 2018KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
26S Proteasome DegradationPathwayWP183 (WikiPathways)
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
APC2GeneProductENSG00000115266 (Ensembl)
APCGeneProduct324 (Entrez Gene)
ARAFGeneProductENSG00000078061 (Ensembl)
ATMGeneProductENSG00000149311 (Ensembl)
ATRGeneProductENSG00000175054 (Ensembl)
AXIN1GeneProduct8312 (Entrez Gene)
AXIN2GeneProductENSG00000168646 (Ensembl)
AngiogenesisPathwayWP1539 (WikiPathways)
BAK1GeneProductENSG00000030110 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BRAFGeneProductENSG00000157764 (Ensembl)
BRCA1GeneProductENSG00000012048 (Ensembl)
BRCA2GeneProductENSG00000139618 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CETN3GeneProductENSG00000153140 (Ensembl)
CSNK1A1GeneProductENSG00000113712 (Ensembl)
CSNK1A1LGeneProductENSG00000180138 (Ensembl)
CSNK2A1GeneProductENSG00000101266 (Ensembl)
CSNK2A2GeneProductENSG00000070770 (Ensembl)
CSNK2A3GeneProductENSG00000254598 (Ensembl)
CSNK2BGeneProductENSG00000204435 (Ensembl)
CTNNB1GeneProduct1499 (Entrez Gene)
Cell CyclePathwayWP179 (WikiPathways)
Cell cycle (G1/S) progressionPathwayWP45 (WikiPathways)
DDB2GeneProductENSG00000134574 (Ensembl)
DLL1GeneProductENSG00000198719 (Ensembl)
DLL3GeneProductENSG00000090932 (Ensembl)
DLL4GeneProductENSG00000128917 (Ensembl)
DVL1GeneProduct1855 (Entrez Gene)
DVL2GeneProduct1856 (Entrez Gene)
DVL3GeneProduct1857 (Entrez Gene)
E2F1GeneProductENSG00000101412 (Ensembl)
E2F2GeneProductENSG00000007968 (Ensembl)
E2F3GeneProductENSG00000112242 (Ensembl)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
ERBB2GeneProductENSG00000141736 (Ensembl)
ESR1GeneProductENSG00000091831 (Ensembl)
ESR2GeneProductENSG00000140009 (Ensembl)
Estradiol-17betaMetaboliteCHEBI:16469 (ChEBI)
Estrogen Signaling PathwayPathway
EstrogenMetaboliteCHEBI:4903 (ChEBI)
FGF10GeneProductENSG00000070193 (Ensembl)
FGF16GeneProductENSG00000196468 (Ensembl)
FGF17GeneProductENSG00000158815 (Ensembl)
FGF18GeneProductENSG00000156427 (Ensembl)
FGF19GeneProductENSG00000162344 (Ensembl)
FGF1GeneProductENSG00000113578 (Ensembl)
FGF20GeneProductENSG00000078579 (Ensembl)
FGF21GeneProductENSG00000105550 (Ensembl)
FGF22GeneProductENSG00000070388 (Ensembl)
FGF23GeneProductENSG00000118972 (Ensembl)
FGF2GeneProductENSG00000138685 (Ensembl)
FGF3GeneProductENSG00000186895 (Ensembl)
FGF4GeneProductENSG00000075388 (Ensembl)
FGF5GeneProductENSG00000138675 (Ensembl)
FGF6GeneProductENSG00000111241 (Ensembl)
FGF7GeneProductENSG00000140285 (Ensembl)
FGF8GeneProductENSG00000107831 (Ensembl)
FGF9GeneProductENSG00000102678 (Ensembl)
FGFR1GeneProductENSG00000077782 (Ensembl)
FLT4GeneProductENSG00000037280 (Ensembl)
FOSGeneProductENSG00000170345 (Ensembl)
FRAT1GeneProductENSG00000165879 (Ensembl)
FRAT2GeneProductENSG00000181274 (Ensembl)
FZD10GeneProduct11211 (Entrez Gene)
FZD1GeneProduct8321 (Entrez Gene)
FZD2GeneProduct2535 (Entrez Gene)
FZD3GeneProduct7976 (Entrez Gene)
FZD4GeneProduct6424 (Entrez Gene)
FZD5GeneProduct7855 (Entrez Gene)
FZD6GeneProduct8323 (Entrez Gene)
FZD7GeneProduct8324 (Entrez Gene)
FZD8GeneProduct8325 (Entrez Gene)
FZD9GeneProduct8326 (Entrez Gene)
GADD45AGeneProductENSG00000116717 (Ensembl)
GADD45BGeneProductENSG00000099860 (Ensembl)
GADD45GGeneProductENSG00000130222 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
GSK3BGeneProduct2932 (Entrez Gene) MOUSE:KG38 MOUSE
HES1GeneProductENSG00000114315 (Ensembl)
HES5GeneProductENSG00000197921 (Ensembl)
HEY1GeneProductENSG00000164683 (Ensembl)
HEY2GeneProductENSG00000135547 (Ensembl)
HEYLGeneProductENSG00000163909 (Ensembl)
HRASGeneProductENSG00000174775 (Ensembl)
IGF1GeneProductENSG00000017427 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
JAG2GeneProductENSG00000184916 (Ensembl)
JUNGeneProductENSG00000177606 (Ensembl)
KITGeneProductENSG00000157404 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl) WHIM9 xenograft has activating mutation in KRAS
LEF1GeneProductENSG00000138795 (Ensembl)
LRP5GeneProductENSG00000162337 (Ensembl)
LRP6GeneProductENSG00000070018 (Ensembl)
MAP2K1GeneProduct5604 (Entrez Gene)
MAP2K2GeneProduct5605 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MRE11AGeneProductENSG00000020922 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
NBNGeneProductENSG00000104320 (Ensembl)
NCOA1GeneProductENSG00000084676 (Ensembl)
NCOA3GeneProductENSG00000124151 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
NOTCH1GeneProductENSG00000148400 (Ensembl)
NOTCH2GeneProductENSG00000134250 (Ensembl)
NOTCH3GeneProductENSG00000074181 (Ensembl)
NOTCH4GeneProductENSG00000204301 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
Notch Signaling PathwayPathwayWP268 (WikiPathways)
PARP1GeneProductENSG00000143799 (Ensembl)
PGRGeneProductENSG00000082175 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
POLKGeneProductENSG00000122008 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
ProgesteroneMetaboliteHMDB01830 (HMDB)
RAD50GeneProductENSG00000113522 (Ensembl)
RAD51GeneProductENSG00000051180 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SHC2GeneProductENSG00000129946 (Ensembl)
SHC3GeneProductENSG00000148082 (Ensembl)
SHC4GeneProductENSG00000185634 (Ensembl)
SKP1GeneProductENSG00000113558 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
SP1GeneProductENSG00000185591 (Ensembl)
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProductENSG00000152284 (Ensembl)
TCF7L2GeneProductENSG00000148737 (Ensembl)
TNFSF11GeneProductENSG00000120659 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
WNT10AGeneProduct80326 (Entrez Gene)
WNT10BGeneProduct7480 (Entrez Gene)
WNT11GeneProduct7481 (Entrez Gene)
WNT16GeneProduct51384 (Entrez Gene)
WNT1GeneProduct7471 (Entrez Gene)
WNT1GeneProductENSG00000125084 (Ensembl)
WNT2GeneProduct7472 (Entrez Gene)
WNT2BGeneProduct7482 (Entrez Gene)
WNT3GeneProduct7473 (Entrez Gene)
WNT3AGeneProduct89780 (Entrez Gene)
WNT4GeneProduct54361 (Entrez Gene)
WNT4GeneProductENSG00000162552 (Ensembl)
WNT5AGeneProduct7474 (Entrez Gene)
WNT5BGeneProduct81029 (Entrez Gene)
WNT6GeneProduct7475 (Entrez Gene)
WNT7AGeneProduct7476 (Entrez Gene)
WNT7BGeneProduct7477 (Entrez Gene)
Wnt Signaling PathwayPathwayWP428 (WikiPathways)
p53 Signaling PathwayPathway

Annotated Interactions

No annotated interactions

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