ILANIT 2023

Glycan-preference characterization of the Fusobacterium nucleatum Fap2 lectin

Ofir Ventura 1 Tamar Alon-Miamon 1 Lei Xia 3 Viviana Scaiewicz 1 Nicole Haj 1 Vered Padler-Karavani 2 Oren Parnas 3 Gilad Bachrach 1
1The Institute of Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, Israel
2Department of Cell Research and Immunology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel
3Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Israel

Fusobacterium nucleatum is an oral bacterium also prevalent in some cancers including colorectal carcinoma (CRC), esophageal and pancreatic cancer. In these cancers, it is associated with poor treatment outcome. It was previously suggested that F. nucleatum can colonize tumors using its lectin Fap2. The aim of this work is to better-characterize the glycans in the host cancer cells that Fap2 binds. Recently we showed that occurrence of F. nucleatum genomic DNA in breast cancer samples correlates with high levels of D-galactose-β (1-3)-N-acetyl-D-galactosamine (Gal-GalNAc). To identify glycans that interact with Fap2 we generated a library of mutant pancreatic cancers cells, and sorted the cells according to their ability of binding Peanut agglutinin (PNA) a Gal-GalNAc lectin using fluorescence activated cell sorting. Preliminary results show that some genes found crucial for the PNA binding, were not critical for binding of F. nucleatum ATCC 23726. However, mutations that caused enhanced binding of PNA, had a similar positive impact on the binding of F. nucleatum ATCC 23726. These genes are essential for the biosynthesis of sialic acids, suggesting that sialic acid hinder the binding of F. nucleatum ATCC 23726 to cancers cells.