Cell genomicsJan 29, 2026

Using CRISPR activation to identify genes involved in cancer sugar molecule changes

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

CRISPR activation screens mapped genes that reshape cancer cell Siglec-binding glycans and pointed to GAL3ST4 as a possible glioma immune-evasion driver.

Evidence

This gain-of-function CRISPRa screening study profiled cancer glycome regulators, including pathways controlling α2-3 sialylation, GlcNAcylation, professional Siglec ligands, CD24 dispensability for Siglec-10 binding, and GAL3ST4 in glioma cells.

Caveat

The evidence is a cell-screening genomic atlas, so therapeutic actionability and immune effects still require validation in more complete cancer models or patients.

Simplified

Many cancers upregulate the expression of sialic acid-containing glycans. These oligosaccharides engage inhibitory sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on immune cells, allowing cancer cells to evade immune surveillance. The genetic mechanisms underlying this process remain poorly defined. In this study, we performed gain-of-function CRISPR activation (CRISPRa) screens to define genetic pathways that regulate expression of Siglec-binding glycans. We show that Siglec ligand expression is controlled through genetic competition between genes that catalyze α2-3 sialylation and GlcNAcylation of galactose residues. Cancer glycome remodeling is also aided by the overexpression of "professional ligands" that facilitate Siglec-glycan binding. Notably, we also find that expression of the CD24 gene is genetically dispensable for cell surface binding of the inhibitory receptor Siglec-10. Finally, we identify the sulfotransferase enzyme GAL3ST4 as a potential driver of immune evasion in glioma cells. Our study provides a unique genomic atlas of cancer-associated glycosylation and identifies immediately actionable targets for cancer immunotherapy.