# CRABP2 promotes metastasis and lipid droplet accumulation in non-small cell lung cancer by downregulating PLAAT4

## TL;DR

This study shows that CRABP2 promotes non-small cell lung cancer progression and lipid droplet accumulation by reducing PLAAT4 levels, suggesting a new therapeutic target.

## Contribution

The study identifies a novel CRABP2/PLAAT4 axis that drives NSCLC progression and metastasis through lipid metabolism.

## Key findings

- CRABP2 expression is elevated in NSCLC tissues and correlates with reduced survival.
- CRABP2 knockdown inhibits NSCLC cell proliferation, migration, invasion, and lipid droplet accumulation.
- CRABP2 binds and destabilizes PLAAT4, and PLAAT4 inhibition reverses CRABP2 knockdown effects.

## Abstract

Non-small cell lung cancer (NSCLC) is a highly prevalent and aggressive cancer with a high incidence. While cellular retinoic acid binding protein 2 (CRABP2) has been implicated in tumor progression, metastasis and drug resistanceacross multiple cancer types, its functional role and molecular mechanisms of CRABP2 in NSCLC progression remain largely unexplored. In this study, we demonstrated that CRABP2 expression was significantly elevated in NSCLC tissues compared to adjacent normal tissues, and high levels of CRABP2 correlated with reduced overall survival. Functionally, knockdown of CRABP2 inhibited NSCLC cell proliferation, migration, and invasion, and lipid droplet accumulation in vitro, while CRABP2 targeting inhibited tumor growth, lipid droplet content and metastasis in xenograft model. Mechanistically, CRABP2 was identified to bind to Phospholipase A/acyltransferase 4 (PLAAT4) and decreases its protein stability. Notably, inhibition of PLAAT4 reverses the shCRABP2-induced suppression of malignant phenotypes and lipid droplet formation. our findings reveal a novel CRABP2/PLAAT4-mediated lipid metabolic axis drives NSCLC progression and metastasis. These findings suggest that targeting CRAPB may offer a novel approach to therapeutic intervention for NSCLC.