Pancreatic adenocarcinoma pathway (WP4263)
Infiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA). Normal duct epithelium progresses to infiltrating cancer through a series of histologically defined precursors, Pancreatic Intraepithelial Neoplasia (PanINs: https://pathology.jhu.edu/pancreas/professionals/DuctLesions.php). The overexpression of HER-2/neu (ERBB2) and activating point mutations in the K-ras gene occur early, inactivation of the p16 gene (CDKN2A) at an intermediate stage, and the inactivation of p53, SMAD4, and BRCA2 occur relatively late. Activated K-ras engages multiple effector pathways. Although EGF receptors are conventionally regarded as upstream activators of RAS proteins, they can also act as RAS signal transducers via RAS-induced autocrine activation of the EGFR family ligands. Moreover, PDA shows extensive genomic instability and aneuploidy. Telomere attrition and mutations in p53 and BRCA2 are likely to contribute to these phenotypes. Inactivation of the SMAD4 tumor suppressor gene leads to loss of the inhibitory influence of the transforming growth factor-beta signaling pathway. The progression of disease and associated mutations is defined based on the arrow at the top, from left to right.
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last edited

Authors

Kristina Hanspers and Egon Willighagen

Cited In

Organism

Homo sapiens

Communities

CPTAC Diseases PancCanNet

Annotations

Pathway Ontology: phosphatidylinositol 3-kinase-Akt signaling pathway cancer pathway disease pathway Jak-Stat signaling pathway

Disease Ontology: pancreatic adenocarcinoma

Cell Type Ontology: pancreatic ductal cell

Participants

Label Type Compact Identifier
PA Metabolite chebi:29089
PIP3 Metabolite chebi:16618
PIP3 Metabolite chebi:16618
DUSP6 GeneProduct ensembl:ENSG00000139318
ARHGEF6 GeneProduct ensembl:ENSG00000129675
PRKCD GeneProduct ensembl:ENSG00000163932
KRAS GeneProduct ensembl:ENSG00000133703
TIAM1 GeneProduct ensembl:ENSG00000156299
RAC1 GeneProduct ensembl:ENSG00000136238
RAC2 GeneProduct ensembl:ENSG00000128340
RAC3 GeneProduct ensembl:ENSG00000169750
PAK4 GeneProduct ensembl:ENSG00000130669
BUB1B-PAK6 GeneProduct ensembl:ENSG00000259288
PAK1 GeneProduct ensembl:ENSG00000149269
PAK2 GeneProduct ensembl:ENSG00000180370
PAK3 GeneProduct ensembl:ENSG00000077264
PAK6 GeneProduct ensembl:ENSG00000137843
PAK5 GeneProduct ensembl:ENSG00000101349
RHOA GeneProduct ensembl:ENSG00000067560
AKT1 GeneProduct ensembl:ENSG00000142208
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
CHUK GeneProduct ensembl:ENSG00000213341
IKBKB GeneProduct ensembl:ENSG00000104365
IKBKG GeneProduct ensembl:ENSG00000269335
NFKB1 GeneProduct ensembl:ENSG00000109320
RELA GeneProduct ncbigene:5970
BAD GeneProduct ensembl:ENSG00000002330
BCL2L1 GeneProduct ensembl:ENSG00000171552
CASP9 GeneProduct ensembl:ENSG00000132906
RAF1 GeneProduct ensembl:ENSG00000132155
MAP2K1 GeneProduct ensembl:ENSG00000169032
MAP2K2 GeneProduct ensembl:ENSG00000126934
MAPK1 GeneProduct ensembl:ENSG00000100030
MAPK3 GeneProduct ensembl:ENSG00000102882
RALGDS GeneProduct ensembl:ENSG00000160271
RALA GeneProduct ensembl:ENSG00000006451
RALB GeneProduct ensembl:ENSG00000144118
PLD1 GeneProduct ensembl:ENSG00000075651
RALBP1 GeneProduct ensembl:ENSG00000017797
RAC1 GeneProduct ensembl:ENSG00000136238
RAC2 GeneProduct ensembl:ENSG00000128340
RAC3 GeneProduct ensembl:ENSG00000169750
CDC42 GeneProduct ensembl:ENSG00000070831
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461
ARAF GeneProduct ensembl:ENSG00000078061
BRAF GeneProduct ensembl:ENSG00000157764
MAPK8 GeneProduct ensembl:ENSG00000107643
MAPK9 GeneProduct ensembl:ENSG00000050748
MAPK10 GeneProduct ensembl:ENSG00000109339
TGFA GeneProduct ensembl:ENSG00000163235
EGF GeneProduct ensembl:ENSG00000138798
EGFR GeneProduct ensembl:ENSG00000146648
ERBB2 GeneProduct ensembl:ENSG00000141736
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
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
RPS6KB1 GeneProduct ensembl:ENSG00000108443
RPS6KB2 GeneProduct ensembl:ENSG00000175634
JAK1 GeneProduct ensembl:ENSG00000162434
STAT1 GeneProduct ensembl:ENSG00000115415
STAT3 GeneProduct ensembl:ENSG00000168610
VEGFA GeneProduct ensembl:ENSG00000112715
TGFB1 GeneProduct ensembl:ENSG00000105329
TGFB2 GeneProduct ensembl:ENSG00000092969
TGFB3 GeneProduct ensembl:ENSG00000119699
TGFBR1 GeneProduct ensembl:ENSG00000106799
TGFBR2 GeneProduct ensembl:ENSG00000163513
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
SMAD4 GeneProduct ensembl:ENSG00000141646
BRCA2 GeneProduct ensembl:ENSG00000139618
RAD51 GeneProduct ensembl:ENSG00000051180
TP53 GeneProduct ensembl:ENSG00000141510
CDKN1A GeneProduct ensembl:ENSG00000124762
BAX GeneProduct ensembl:ENSG00000087088
DDB2 GeneProduct ensembl:ENSG00000134574
GADD45A GeneProduct ensembl:ENSG00000116717
GADD45B GeneProduct ensembl:ENSG00000099860
GADD45G GeneProduct ensembl:ENSG00000130222
BAK1 GeneProduct ensembl:ENSG00000030110
POLK GeneProduct ensembl:ENSG00000122008
CDKN2A GeneProduct ensembl:ENSG00000147889
CDK4 GeneProduct ensembl:ENSG00000135446
CDK6 GeneProduct ensembl:ENSG00000105810
CCND1 GeneProduct ensembl:ENSG00000110092
RB1 GeneProduct ensembl:ENSG00000139687
E2F1 GeneProduct ensembl:ENSG00000101412
E2F2 GeneProduct ensembl:ENSG00000007968
E2F3 GeneProduct ensembl:ENSG00000112242
RIPK4 GeneProduct ensembl:ENSG00000183421
PEBP1 GeneProduct ensembl:ENSG00000089220
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References

  1. Furukawa T, Sunamura M, Motoi F, Matsuno S, Horii A. Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer. Am J Pathol. 2003 Jun;162(6):1807–15. PubMed Europe PMC Scholia
  2. Qi Z-H, Xu H-X, Zhang S-R, Xu J-Z, Li S, Gao H-L, et al. RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. Int J Oncol. 2018 Apr;52(4):1105–16. PubMed Europe PMC Scholia
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