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. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
AuthorsKristina Hanspers and Egon Willighagen
Discuss this pathway
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
OrganismsHomo sapiens CPTAC Diseases PancCanNet
Pathway Ontologycancer pathway Jak-Stat signaling pathway phosphatidylinositol 3-kinase-Akt signaling pathway disease pathway
Cell Type Ontologypancreatic ductal cell
Disease Ontologypancreatic adenocarcinoma
- Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer. Furukawa T, Sunamura M, Motoi F, Matsuno S, Horii A. Am J Pathol. 2003 Jun;162(6):1807–15. PubMed Europe PMC Scholia
- PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
- RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. Qi ZH, Xu HX, Zhang SR, Xu JZ, Li S, Gao HL, et al. Int J Oncol. 2018 Apr;52(4):1105–16. PubMed Europe PMC Scholia