Pancreatic adenocarcinoma pathway (Homo sapiens)

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21Pancreatic ductal cellNucleusGrowth inhibitionNormal ductCell survivalDS DNA break repairAngiogenesisPanIN-1AAnti-apoptotic genesVEGF SignalingPathwayPRKCDARHGEF6ERBB SignalingPathwayPADUSP6ApoptosisPI3K-Akt SignalingPIP3KRASTIAM1RAC1RAC2RAC3PAK4BUB1B-PAK6PAK1PAK2PAK3PAK6PAK5RHOACytoskeleton organizationCell motilityAKT1AKT2AKT3CHUKPIKBKBIKBKGPNFKB1RELABADPBCL2L1CASP9PRAF1MAP2K1MAP2K2PPPPMAPK1PPMAPK3PPProliferative genesRALGDSRALARALBPLD1RALBP1RAC1RAC2RAC3CDC42PIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3Supressed apoptosisARAFBRAFMAPK8MAPK9MAPK10TGFAEGFEGFRERBB2+PIK3CAPIK3CBPIK3CDPIK3R1PIK3R2PIK3R3PIP3AKT1AKT2AKT3MTORRPS6KB1PRPS6KB2JAK1STAT1STAT3PVEGFATGFB1TGFB2TGFB3TGFBR1TGFBR2SMAD2SMAD3SMAD4BRCA2RAD51TP53DNA damageCDKN1ABAXDDB2GADD45AGADD45BGADD45GBAK1POLKCDKN2ACDK4CDK6CCND1RB1E2F1E2F2E2F3G1/S Cell Cycle ControlAdenocarcinomaLegendActivating mutationInactivating mutationCell cycleTGFb SignalingPathwayPanIN-1BPanIN-2PanIN-3RIPK4PEBP1+Amplification


Description

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.

Source: KEGG http://www.genome.jp/kegg-bin/show_pathway?map05212

Quality Tags

Ontology Terms

 

Bibliography

  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 PubMed Europe PMC
  2. Qi ZH, Xu HX, Zhang SR, Xu JZ, Li S, Gao HL, Jin W, Wang WQ, Wu CT, Ni QX, Yu XJ, Liu L; ''RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling.''; Int J Oncol, 2018 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
105482view05:38, 8 August 2019KhanspersModified description
105445view04:56, 8 August 2019KhanspersModified description
105005view04:56, 28 June 2019KhanspersModified description
103768view00:26, 5 April 2019Khanspersupdated ERBB2 status and legend
97005view23:27, 25 April 2018KhanspersModified title
96948view06:21, 21 April 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
96946view20:43, 20 April 2018KhanspersModified title
96945view20:42, 20 April 2018KhanspersOntology Term : 'pancreatic ductal cell' added !
96944view20:41, 20 April 2018KhanspersModified description
96943view20:40, 20 April 2018Khanspersadded PKCG/RIPK4/PEBP1 module, and DUSP6
96942view20:03, 20 April 2018Khanspersupdated p16 label
96940view19:32, 20 April 2018Khansperslayout and update of progression graphic
96939view19:28, 20 April 2018Khanspersupdated layout
96938view19:27, 20 April 2018KhanspersModified description
96935view19:22, 20 April 2018KhanspersOntology Term : 'disease pathway' added !
96934view19:22, 20 April 2018KhanspersOntology Term : 'cancer pathway' added !
96933view19:22, 20 April 2018KhanspersOntology Term : 'Jak-Stat signaling pathway' added !
96932view19:22, 20 April 2018KhanspersModified title
96931view19:21, 20 April 2018KhanspersOntology Term : 'phosphatidylinositol 3-kinase-Akt signaling pathway' added !
96930view19:21, 20 April 2018KhanspersOntology Term : 'pancreatic adenocarcinoma' added !
96929view18:29, 20 April 2018KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ARAFGeneProductENSG00000078061 (Ensembl)
ARHGEF6GeneProductENSG00000129675 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
BADGeneProductENSG00000002330 (Ensembl)
BAK1GeneProductENSG00000030110 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BCL2L1GeneProductENSG00000171552 (Ensembl)
BRAFGeneProductENSG00000157764 (Ensembl)
BRCA2GeneProductENSG00000139618 (Ensembl)
BUB1B-PAK6GeneProductENSG00000259288 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CDKN2AGeneProductENSG00000147889 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
Cell cyclePathwayWP179 (WikiPathways)
DDB2GeneProductENSG00000134574 (Ensembl)
DUSP6GeneProductENSG00000139318 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
E2F2GeneProductENSG00000007968 (Ensembl)
E2F3GeneProductENSG00000112242 (Ensembl)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
ERBB Signaling PathwayPathwayWP673 (WikiPathways)
ERBB2GeneProductENSG00000141736 (Ensembl)
G1/S Cell Cycle ControlPathwayWP45 (WikiPathways)
GADD45AGeneProductENSG00000116717 (Ensembl)
GADD45BGeneProductENSG00000099860 (Ensembl)
GADD45GGeneProductENSG00000130222 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
JAK1GeneProductENSG00000162434 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK10GeneProductENSG00000109339 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
MAPK9GeneProductENSG00000050748 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
PAMetaboliteCHEBI:29089 (ChEBI)
PAK1GeneProductENSG00000149269 (Ensembl)
PAK2GeneProductENSG00000180370 (Ensembl)
PAK3GeneProductENSG00000077264 (Ensembl)
PAK4GeneProductENSG00000130669 (Ensembl)
PAK5GeneProductENSG00000101349 (Ensembl)
PAK6GeneProductENSG00000137843 (Ensembl)
PEBP1GeneProductENSG00000089220 (Ensembl)
PI3K-Akt SignalingPathwayWP4172 (WikiPathways)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLD1GeneProductENSG00000075651 (Ensembl)
POLKGeneProductENSG00000122008 (Ensembl)
PRKCDGeneProductENSG00000163932 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
RAC2GeneProductENSG00000128340 (Ensembl)
RAC3GeneProductENSG00000169750 (Ensembl)
RAD51GeneProductENSG00000051180 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RALAGeneProductENSG00000006451 (Ensembl)
RALBGeneProductENSG00000144118 (Ensembl)
RALBP1GeneProductENSG00000017797 (Ensembl)
RALGDSGeneProductENSG00000160271 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RELAGeneProduct5970 (Entrez Gene)
RHOAGeneProductENSG00000067560 (Ensembl)
RIPK4GeneProductENSG00000183421 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
STAT1GeneProductENSG00000115415 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
TGFAGeneProductENSG00000163235 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TGFB2GeneProductENSG00000092969 (Ensembl)
TGFB3GeneProductENSG00000119699 (Ensembl)
TGFBR1GeneProductENSG00000106799 (Ensembl)
TGFBR2GeneProductENSG00000163513 (Ensembl)
TGFb Signaling PathwayPathway
TIAM1GeneProductENSG00000156299 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
VEGF Signaling PathwayPathway
VEGFAGeneProductENSG00000112715 (Ensembl)

Annotated Interactions

No annotated interactions

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