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.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

CRISPR Gene EditingIssue #22

CRISPR editors hit 50% efficiency in eye cells, plus new tools tackle cancer DNA and crop improvement

↗

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

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief