Breast cancer pathway (WP4262)

Homo sapiens

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.

Authors

Kristina Hanspers , Egon Willighagen , Irene Hemel , Friederike Ehrhart , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

CPTAC Diseases

Annotations

Disease Ontology

cancer

Pathway Ontology

phosphatidylinositol 3-kinase-Akt signaling pathway cancer pathway Notch signaling pathway disease pathway breast cancer pathway

Participants

Label Type Compact URI Comment
Estrogen Metabolite chebi:4903
PIP3 Metabolite chebi:16618
Progesterone Metabolite hmdb:HMDB0001830
Estrogen Metabolite chebi:4903
Progesterone Metabolite hmdb:HMDB0001830
Estrogen Metabolite chebi:4903
Progesterone Metabolite hmdb:HMDB0001830
Estrogen Metabolite chebi:4903
Estradiol-17beta Metabolite chebi:16469
ATR GeneProduct ensembl:ENSG00000175054
HES1 GeneProduct ensembl:ENSG00000114315
FGF1 GeneProduct ensembl:ENSG00000113578
CETN3 GeneProduct ensembl:ENSG00000153140
TCF7 GeneProduct ensembl:ENSG00000081059
CDK4 GeneProduct ensembl:ENSG00000135446
FGF20 GeneProduct ensembl:ENSG00000078579
PARP1 GeneProduct ensembl:ENSG00000143799
FGF23 GeneProduct ensembl:ENSG00000118972
FGF16 GeneProduct ensembl:ENSG00000196468
PTEN GeneProduct ensembl:ENSG00000171862
FGF7 GeneProduct ensembl:ENSG00000140285
BRCA1 GeneProduct ensembl:ENSG00000012048
MRE11A GeneProduct ensembl:ENSG00000020922
SKP1 GeneProduct ensembl:ENSG00000113558
RAD51 GeneProduct ensembl:ENSG00000051180
FGF5 GeneProduct ensembl:ENSG00000138675
ATM GeneProduct ensembl:ENSG00000149311
FGF6 GeneProduct ensembl:ENSG00000111241
ERBB2 GeneProduct ensembl:ENSG00000141736
FGF17 GeneProduct ensembl:ENSG00000158815
GRB2 GeneProduct ensembl:ENSG00000177885
HEY1 GeneProduct ensembl:ENSG00000164683
FGF21 GeneProduct ensembl:ENSG00000105550
RPS6KB1 GeneProduct ensembl:ENSG00000108443
FGF18 GeneProduct ensembl:ENSG00000156427
FGF19 GeneProduct ensembl:ENSG00000162344
TP53 GeneProduct ensembl:ENSG00000141510
FGFR1 GeneProduct ensembl:ENSG00000077782
IGF1R GeneProduct ensembl:ENSG00000140443
IGF1 GeneProduct ensembl:ENSG00000017427
SHC1 GeneProduct ensembl:ENSG00000160691
SHC2 GeneProduct ensembl:ENSG00000129946
SHC3 GeneProduct ensembl:ENSG00000148082
SHC4 GeneProduct ensembl:ENSG00000185634
SOS1 GeneProduct ensembl:ENSG00000115904
SOS2 GeneProduct ensembl:ENSG00000100485
HRAS GeneProduct ensembl:ENSG00000174775
KRAS GeneProduct ensembl:ENSG00000133703 WHIM9 xenograft has activating mutation in KRAS
NRAS GeneProduct ensembl:ENSG00000213281
ARAF GeneProduct ensembl:ENSG00000078061
BRAF GeneProduct ensembl:ENSG00000157764
RAF1 GeneProduct ensembl:ENSG00000132155
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461
AKT1 GeneProduct ensembl:ENSG00000142208
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
MTOR GeneProduct ensembl:ENSG00000198793
RPS6KB2 GeneProduct ensembl:ENSG00000175634
EGF GeneProduct ensembl:ENSG00000138798
EGFR GeneProduct ensembl:ENSG00000146648
KIT GeneProduct ensembl:ENSG00000157404
JAG2 GeneProduct ensembl:ENSG00000184916
NOTCH1 GeneProduct ensembl:ENSG00000148400
NOTCH2 GeneProduct ensembl:ENSG00000134250
NOTCH3 GeneProduct ensembl:ENSG00000074181
NOTCH4 GeneProduct ensembl:ENSG00000204301
DLL1 GeneProduct ensembl:ENSG00000198719
DLL3 GeneProduct ensembl:ENSG00000090932
DLL4 GeneProduct ensembl:ENSG00000128917
LRP5 GeneProduct ensembl:ENSG00000162337
LRP6 GeneProduct ensembl:ENSG00000070018
FRAT1 GeneProduct ensembl:ENSG00000165879
FRAT2 GeneProduct ensembl:ENSG00000181274
TCF7L2 GeneProduct ensembl:ENSG00000148737
TCF7L1 GeneProduct ensembl:ENSG00000152284
LEF1 GeneProduct ensembl:ENSG00000138795
MYC GeneProduct ensembl:ENSG00000136997
CCND1 GeneProduct ensembl:ENSG00000110092
ERBB2 GeneProduct ensembl:ENSG00000141736
FLT4 GeneProduct ensembl:ENSG00000037280
HEY2 GeneProduct ensembl:ENSG00000135547
HEYL GeneProduct ensembl:ENSG00000163909
HES5 GeneProduct ensembl:ENSG00000197921
CCND1 GeneProduct ensembl:ENSG00000110092
MYC GeneProduct ensembl:ENSG00000136997
ERBB2 GeneProduct ensembl:ENSG00000141736
CDKN1A GeneProduct ensembl:ENSG00000124762
NFKB2 GeneProduct ensembl:ENSG00000077150
BRCA2 GeneProduct ensembl:ENSG00000139618
CDKN1A GeneProduct ensembl:ENSG00000124762
BAX GeneProduct ensembl:ENSG00000087088
DDB2 GeneProduct ensembl:ENSG00000134574
POLK GeneProduct ensembl:ENSG00000122008
BAK1 GeneProduct ensembl:ENSG00000030110
GADD45G GeneProduct ensembl:ENSG00000130222
GADD45A GeneProduct ensembl:ENSG00000116717
GADD45B GeneProduct ensembl:ENSG00000099860
CDK6 GeneProduct ensembl:ENSG00000105810
RB1 GeneProduct ensembl:ENSG00000139687
E2F1 GeneProduct ensembl:ENSG00000101412
E2F2 GeneProduct ensembl:ENSG00000007968
E2F3 GeneProduct ensembl:ENSG00000112242
ESR1 GeneProduct ensembl:ENSG00000091831
ESR2 GeneProduct ensembl:ENSG00000140009
PGR GeneProduct ensembl:ENSG00000082175
ESR1 GeneProduct ensembl:ENSG00000091831
ESR2 GeneProduct ensembl:ENSG00000140009
PGR GeneProduct ensembl:ENSG00000082175
ESR1 GeneProduct ensembl:ENSG00000091831
ESR2 GeneProduct ensembl:ENSG00000140009
PGR GeneProduct ensembl:ENSG00000082175
NCOA3 GeneProduct ensembl:ENSG00000124151
NCOA1 GeneProduct ensembl:ENSG00000084676
WNT1 GeneProduct ensembl:ENSG00000125084
WNT4 GeneProduct ensembl:ENSG00000162552
TNFSF11 GeneProduct ensembl:ENSG00000120659
NCOA3 GeneProduct ensembl:ENSG00000124151
NCOA1 GeneProduct ensembl:ENSG00000084676
ESR1 GeneProduct ensembl:ENSG00000091831
ESR2 GeneProduct ensembl:ENSG00000140009
MYC GeneProduct ensembl:ENSG00000136997
CCND1 GeneProduct ensembl:ENSG00000110092
CCND1 GeneProduct ensembl:ENSG00000110092
NCOA3 GeneProduct ensembl:ENSG00000124151
NCOA1 GeneProduct ensembl:ENSG00000084676
ESR1 GeneProduct ensembl:ENSG00000091831
ESR2 GeneProduct ensembl:ENSG00000140009
FOS GeneProduct ensembl:ENSG00000170345
JUN GeneProduct ensembl:ENSG00000177606
SP1 GeneProduct ensembl:ENSG00000185591
FGF2 GeneProduct ensembl:ENSG00000138685
FGF3 GeneProduct ensembl:ENSG00000186895
FGF4 GeneProduct ensembl:ENSG00000075388
FGF8 GeneProduct ensembl:ENSG00000107831
FGF9 GeneProduct ensembl:ENSG00000102678
FGF10 GeneProduct ensembl:ENSG00000070193
FGF22 GeneProduct ensembl:ENSG00000070388
APC2 GeneProduct ensembl:ENSG00000115266
DVL3 GeneProduct ncbigene:1857
GSK3B GeneProduct ncbigene:2932 MOUSE:KG38 MOUSE
CSNK2B GeneProduct ensembl:ENSG00000204435
APC GeneProduct ncbigene:324
CSNK1A1 GeneProduct ensembl:ENSG00000113712
DVL2 GeneProduct ncbigene:1856
CSNK2A1 GeneProduct ensembl:ENSG00000101266
AXIN1 GeneProduct ncbigene:8312
DVL1 GeneProduct ncbigene:1855
CSNK1A1L GeneProduct ensembl:ENSG00000180138
CSNK2A3 GeneProduct ensembl:ENSG00000254598
CSNK2A2 GeneProduct ensembl:ENSG00000070770
CTNNB1 GeneProduct ncbigene:1499
AXIN2 GeneProduct ensembl:ENSG00000168646
CTNNB1 GeneProduct ncbigene:1499
FZD3 GeneProduct ncbigene:7976
FZD8 GeneProduct ncbigene:8325
FZD10 GeneProduct ncbigene:11211
FZD7 GeneProduct ncbigene:8324
FZD4 GeneProduct ncbigene:6424
FZD1 GeneProduct ncbigene:8321
FZD6 GeneProduct ncbigene:8323
FZD5 GeneProduct ncbigene:7855
FZD9 GeneProduct ncbigene:8326
FZD2 GeneProduct ncbigene:2535
WNT3A GeneProduct ncbigene:89780
WNT7A GeneProduct ncbigene:7476
WNT11 GeneProduct ncbigene:7481
WNT1 GeneProduct ncbigene:7471
WNT5B GeneProduct ncbigene:81029
WNT2 GeneProduct ncbigene:7472
WNT2B GeneProduct ncbigene:7482
WNT6 GeneProduct ncbigene:7475
WNT5A GeneProduct ncbigene:7474
WNT16 GeneProduct ncbigene:51384
WNT4 GeneProduct ncbigene:54361
WNT3 GeneProduct ncbigene:7473
WNT10B GeneProduct ncbigene:7480
WNT7B GeneProduct ncbigene:7477
WNT10A GeneProduct ncbigene:80326
WNT16 GeneProduct ncbigene:51384
MAP2K1 GeneProduct ncbigene:5604
MAPK1 GeneProduct ncbigene:5594
MAPK3 GeneProduct ncbigene:5595
MAP2K2 GeneProduct ncbigene:5605
RAD50 GeneProduct ensembl:ENSG00000113522
NBN GeneProduct ensembl:ENSG00000104320

References

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