Impact of the LINE-1 retrotransposon on pancreatic circulating tumor cells

• Applicant: Dr. Katarina Ondrejkova
• Subject Area: Gastroenterology ; Hematology, Oncology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570854358

The aim of this project is to investigate the distinct roles of the LINE-1 retrotransposon, specifically the proteins ORF1p and ORF2p, in epithelial-mesenchymal transition (EMT), metastasis, and the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). A better understanding of the molecular mechanisms by which the LINE-1 retrotransposon influences tumor progression and metastasis could open new options for the development of therapeutic strategies and biomarkers for PDAC patients. In previous work of Prof. David Ting's research group, a connection between LINE-1 expression and epithelial-mesenchymal transition (EMT) in PDAC tumor cells and circulating tumor cells (CTCs) was demonstrated. It was shown that CTCs isolated from PDAC patients exhibit higher LINE-1 expression compared to primary tumor cells. These findings suggest that the LINE-1 retrotransposon may play a key role in the onset of EMT and the ability of tumor cells to metastasize. Another central aim of the project is to investigate the specific functions of the two LINE-1 proteins, ORF1p and ORF2p. It is hypothesized that ORF1p and ORF2p play distinct, independent roles. This investigation could provide new therapeutic approaches for combating metastasis in PDAC by selectively targeting individual components of the LINE-1 retrotransposon. The planned experiments build on the established and optimized models of Prof. Ting's research group. Using 3D cell culture models, isolated CTCs, and single-cell RNA sequencing, the role of the LINE-1 retrotransposon and its two proteins ORF1p and ORF2p will be further characterized. Specifically, the project will investigate how these proteins influence EMT plasticity in tumor cells and their ability to metastasize. Additionally, the potential of LINE-1 as a biomarker for prognosis and response to therapies in PDAC patients will be explored. In the long term, the project aims to identify new therapeutic targets that are directed at the components of LINE-1, thereby expanding treatment options for PDAC. Furthermore, it seeks to contribute to the improvement of early detection, prognosis, and quality of life, particularly for operable PDAC patients.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. David Ting