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 R2 > 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.
Highlights
Pancreatic adenocarcinoma is the seventh leading cause of cancer-related deaths worldwide [1]
This study shows for the first time that IMP2 expression is linked to progression and poor survival in pancreatic cancer
IMP2 Is Overexpressed in Precursor Lesions, pancreatic ductal adenocarcinoma (PDAC) and Linked to Lower Rate of Survival
Summary
Pancreatic adenocarcinoma is the seventh leading cause of cancer-related deaths worldwide [1]. Insulin-like growth factor 2 (IGF2) mRNA binding proteins (IGF2BPs/IMPs) have been described to be oncogenic in several types of cancer including pancreatic cancer [2,3,4,5,6,7]. The IMP family member IMP3 has originally been identified and pancreatic cancer tissues [8] and studied in this cancer type in more detail compared to the other two IMPs [9,10,11,12]. In lung cancer IMP1 has been reported to increase Kras signaling [13], which is frequently altered in pancreatic cancer tissue. IMP2 has been reported to be the most abundant of the three members of the IMP family in most cancer types including pancreatic ductal adenocarcinoma (PDAC) [5]. Beside gene expression in pancreatic cancer samples of the TCGA data set little is known about its role in pancreatic cancer progression and its prognostic relevance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
