Deacetylated Sialic Acids Increases Selectin‐binding in Lung Cancer Cells

Abstract

Cancers utilize glycans to evade the immune system via the Sialic acid‐ Selectin pathway. Sialic acid specifically uses E‐ selectins, P‐ selectins, and L‐ selectins which each have different properties and preferred ligands. Here, we focused on modulating 9‐O and 7, 9‐O‐acetylation of Neu5Ac, via CRISPR‐ Cas9 gene editing, a functional group that is absent from Sias on many types of cancer cells. The two genes that are responsible for regulating the level of acetylation on Neu5Ac, are Sialic acid acetylesterase (SIAE) and Sialic acid acetyltransferase (CASD1). These genes modulated Selectin binding in lung cancer cells. In the absence of SIAE, Neu5Ac is acetylated, and binding of selectins is slightly increased whereas binding was greatly increased when the ability to acetylate was removed via CASD1 knock out. In addition to modulation Selectin binding, the absence of CASD1 knock out showed a greater expression of both PSGL‐1 (P‐selectin glycoprotein ligand) and Sialyl‐Lewisx. These glycans are essential ligands for P‐ and L‐ selectins, respectively. We are currently working on migration data to see how the modulation of Sialic acid contributes to the metastatic property of lung cancer. Uncovering how functional group alterations on Neu5Ac contribute mechanistically to both Selectin receptor binding, the Sialic Acid‐Selectin immune evasion pathway, Selectin‐receptor mediated migration, and the production of cancer‐associated selectin ligands—offers a promising avenue for targeted cancer immune therapies in the future.