Breast cancer pathway (Homo sapiens)

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Hereditary breast cancerATRScaffold95Legend+NucleusDNA damageTranscriptional regulationLuminal ADS breakNOTCH1 intracellular cytoplasmic domain translocationProliferationProliferationSurvivalTranslationActivating mutationUncontrolled proliferationIncreased survivalGenomic instabilityHES1Estrogen signalingpathwayWnt signaling pathwayFGF1AngiogenesisCETN3TCF7Notch signalingpathwayCDK4FGF20PARP1FGF23FGF16EstrogenPTENFGF77Cell cycleBRCA1MRE11ASKP1PIP3RAD51FGF5ProgesteroneATMFGF6ERBB2+1, 2Cell cycle (G1/S) progressionFGF17GRB2HEY1p53 signalingpathwayFGF21RPS6KB1FGF18FGF19TP53FGFR110, 11+IGF1RIGF1SHC1SHC2SHC3SHC4SOS1SOS2HRASKRAS8NRASARAFBRAFRAF1PIK3CA3, 4, 6, 7PIK3CDPIK3R1PIK3R2PIK3R3AKT1AKT2AKT3MTORRPS6KB2EGFEGFRKITJAG2NOTCH1NOTCH2NOTCH3NOTCH4DLL1DLL3DLL4LRP5LRP6FRAT1FRAT2TCF7L2TCF7L1LEF1MYCCCND1ERBB2FLT4HEY2HEYLHES5CCND1MYCERBB2CDKN1ANFKB2BRCA2Error-prone repair ofdouble-strand breaksChromosomal instabilityCDKN1ABAXDDB2POLKBAK1GADD45GGADD45AGADD45BCDK6RB1PE2F1E2F2E2F3ESR1ESR2PGRESR1ESR2EstrogenPGRProgesteroneESR1ESR2EstrogenPGRProgesteroneNCOA3NCOA1WNT1WNT4TNFSF11NCOA3NCOA1ESR1ESR2EstrogenMYCCCND1CCND1NCOA3NCOA1ESR1ESR2Estradiol-17betaFOSJUNSP1Inactivating mutationFGF2FGF3FGF4FGF8FGF9FGF10FGF22APC2DVL3GSK3BCSNK2BAPCCSNK1A1DVL2CSNK2A1AXIN1DVL1CSNK1A1LCSNK2A3CSNK2A2CTNNB1AXIN2CTNNB1PPPFZD326S proteasome degradationFZD8FZD10FZD7FZD4FZD1FZD6FZD5FZD9FZD2WNT3AWNT7AWNT11WNT1WNT5BWNT2WNT2BWNT6WNT5AWNT16WNT4WNT3WNT10BWNT7BWNT10AWNT16MAP2K1PPMAPK1PPMAPK3PPMAP2K2PPRAD50NBNLuminal BHER2 positiveBasal-like / triple negativeAmplification


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. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

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Bibliography

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  1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL; ''Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.''; Science, 1987 PubMed Europe PMC Scholia
  2. Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, Monsey J, Goel N, Aronson AB, Li S, Ma CX, Ding L, Mardis ER, Ellis MJ; ''Activating HER2 mutations in HER2 gene amplification negative breast cancer.''; Cancer Discov, 2013 PubMed Europe PMC Scholia
  3. Mukohara T; ''PI3K mutations in breast cancer: prognostic and therapeutic implications.''; Breast Cancer (Dove Med Press), 2015 PubMed Europe PMC Scholia
  4. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmström PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R; ''PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma.''; Cancer Res, 2005 PubMed Europe PMC Scholia
  5. 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 Europe PMC Scholia
  6. O'Brien C, Wallin JJ, Sampath D, GuhaThakurta D, Savage H, Punnoose EA, Guan J, Berry L, Prior WW, Amler LC, Belvin M, Friedman LS, Lackner MR; ''Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.''; Clin Cancer Res, 2010 PubMed Europe PMC Scholia
  7. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT; ''An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.''; Cancer Res, 2008 PubMed Europe PMC Scholia
  8. 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 Europe PMC Scholia
  9. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia
  10. 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 Europe PMC Scholia
  11. Hynes NE, Dey JH; ''Potential for targeting the fibroblast growth factor receptors in breast cancer.''; Cancer Res, 2010 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128640view19:32, 17 February 2024EweitzEconomize layout
128638view14:59, 17 February 2024EweitzRefine luminal B demarcation
128637view14:55, 17 February 2024EweitzEconomize layout
128636view14:27, 17 February 2024EweitzEconomize layout
128635view14:04, 17 February 2024EweitzIdentify pathway, economize layout, standardize case
127350view17:58, 20 September 2023Khanspersupdated phospho sites
127317view23:23, 12 September 2023Khanspersupdated phosphosites
127229view20:06, 25 August 2023Khanspersadded ref and updated description
126530view23:03, 25 May 2023Khanspersupdated phosphorylation interaction type
123349view10:43, 17 July 2022EgonwMade six pathways clickable
108103view10:16, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
108060view13:00, 27 November 2019FehrhartOntology Term : 'cancer' added !
106787view13:26, 17 September 2019MaintBotHMDB identifier normalization
105490view05:45, 8 August 2019KhanspersModified description
105474view05:20, 8 August 2019KhanspersModified description
105329view23:37, 30 July 2019Khanspersupdated interactions and links
105006view04:56, 28 June 2019KhanspersModified description
104846view14:37, 20 June 2019IreneHemelChanged undirected interaction between RB1 and E2F to binding
103781view20:26, 5 April 2019Khanspersmoved lit refs from state to parent node
103769view00:49, 5 April 2019Khanspersupdated mutation/amplification states and added to legend
103745view21:20, 2 April 2019Khanspersadded subtypes
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

View all...
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 cycle (G1/S) progressionPathwayWP45 (WikiPathways)
Cell cyclePathwayWP179 (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 pathwayPathwayWP712 (WikiPathways)
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)
ProgesteroneMetaboliteHMDB0001830 (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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