Please use this identifier to cite or link to this item: doi:10.22028/D291-28241
Title: The Insulin-Like Growth Factor 2 mRNA Binding Protein IMP2/IGF2BP2 is Overexpressed and Correlates with Poor Survival in Pancreatic Cancer
Author(s): Dahlem, Charlotte
Barghash, Ahmad
Puchas, Philip
Haybaeck, Johannes
Kessler, Sonja M.
Language: English
Title: International Journal of Molecular Sciences
Volume: 20
Issue: 13
Publisher/Platform: MDPI
Year of Publication: 2019
Free key words: p62
DDC notations: 500 Science
610 Medicine and health
Publikation type: Journal Article
Abstract: The insulin-like growth factor 2 (IGF2) mRNA binding protein IMP2 (IGF2BP2) is an oncogenic protein known to be overexpressed in different tumor types. Pancreatic cancer is a very lethal cancer that requires early diagnosis and new treatment options. The aim of our study was to investigate the role of IMP2 in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). IMP2 was significantly overexpressed in a human precursor (PanIN) lesions suggesting IMP2 as a marker for early stages of PDAC. In a PDAC cohort of matched normal and tumor samples IMP2 showed overexpression in tumor tissues compared with normal pancreatic tissue. Strict correlation analysis (threshold R 2 > 0.75) revealed 22 genes highly positively and 9 genes highly negatively correlating with IMP2. Besides genes involved in the inhibition of apoptosis (Bcl-XL), especially factors involved in ubiquitination were strongly correlated with IMP2 expression: SMURF1 and FBXO45. Moreover, protein kinase C (PKC) signaling pathway was distinctly affected: DXS1179E encoding PKC iota, PKC substrate PLEK2, and inositol triphosphate receptor IP3R3 were positively correlated with IMP2 expression. Besides tumor initiation, IMP2 also seemed to have an impact on tumor progression. TGF-β treatment of Panc-1 pancreatic cancer cells to induce epithelial-mesenchymal transition (EMT) was accompanied by increased IMP2 expression. EMT is important for cancer cells to gain migratory and invasive potential, which is essential for metastasis. Concordantly, circulating tumor cells showed higher IMP2 levels as compared with normal tissue from tumor origin and with normal hematological cells. Accordingly, IMP2 protein levels correlated with poor survival. In conclusion, as IMP2 seems to promote tumor progression of PDAC, it might be an interesting diagnostic and prognostic marker as well as a novel target for the treatment of PDAC.
DOI of the first publication: 10.3390/ijms20133204
Link to this record: urn:nbn:de:bsz:291--ds-282417
ISSN: 1422-0067
Date of registration: 13-Nov-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Alexandra K. Kiemer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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