# β1,4-galactosyltransferase III drives retinoblastoma invasion via activation of integrin-FAK axis

## TL;DR

This study identifies B4GALT3 as a driver of retinoblastoma invasion and shows that inhibiting it could be a new treatment strategy.

## Contribution

The study reveals a novel role of B4GALT3 in retinoblastoma progression via integrin-FAK signaling and identifies a potential inhibitor.

## Key findings

- B4GALT3 enhances retinoblastoma cell proliferation and invasion by promoting integrin glycosylation and FAK signaling.
- Myricoside, a B4GALT3 inhibitor, suppresses retinoblastoma malignancy in vitro and in vivo.
- B4GALT3 inhibition disrupts retinal epithelial barriers by reducing MMP2 expression.

## Abstract

Retinoblastoma (RB) is the most common primary intraocular malignancy in children, and its extraocular extension is closely linked to poor prognosis. However, the molecular drivers underlying local invasion remain incompletely defined. Here, we identify β‑1,4‑galactosyltransferase III (B4GALT3) as a glycosyltransferase selectively upregulated in highly proliferative MKI67⁺ RB subpopulations. B4GALT3 promotes RB cell proliferation, fibronectin adhesion, and invasion by enhancing β1-integrin glycosylation, thereby activating FAK signaling and inducing MMP2 expression to disrupt retinal epithelial barriers. Genetic modulation of B4GALT3 significantly altered both tumor burden and invasive behavior in orthotopic xenograft models. Structure-based virtual screening identified myricoside as a B4GALT3 inhibitor, which suppressed RB malignancy in vitro and in vivo. Overall, our findings uncover a B4GALT3–integrin–FAK axis as a key regulator of RB progression and highlight B4GALT3 inhibition as a promising therapeutic strategy for advanced RB.