# LMO4 promotes OSCC progression by inducing RAB17 degradation and ferroptosis resistance

## TL;DR

The protein LMO4 helps oral cancer cells grow and resist cell death by reducing RAB17 levels, suggesting a new target for treatment.

## Contribution

This study reveals a novel role of LMO4 in promoting oral cancer progression via RAB17 degradation and ferroptosis resistance.

## Key findings

- LMO4 expression is elevated in oral cancer tissues and correlates with worse survival.
- LMO4 promotes cancer cell growth and resistance to ferroptosis by degrading RAB17.
- Restoring RAB17 reduces malignant behaviors in oral cancer cells.

## Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited improvement in patient outcomes despite advances in surgery, chemotherapy, and radiotherapy. The LIM-only protein LMO4 functions as a transcriptional co-regulator and is known to be increased in several epithelial cancers, but its contribution to OSCC has not been well defined. In this study, we found that LMO4 expression was markedly higher in OSCC tissues and was associated with poorer overall survival. Cellular experiments showed that LMO4 enhanced OSCC cell proliferation, migration, and resistance to ferroptosis by promoting the ubiquitin–proteasome–dependent degradation of the tumor suppressor RAB17. Restoration of RAB17 expression reduced these malignant behaviors. In a nude mouse xenograft model, tumors with high LMO4 grew faster and displayed lower RAB17 protein levels. Taken together, our results indicate that LMO4 contributes to OSCC progression through post-translational regulation of RAB17 and ferroptosis control, suggesting that this pathway could serve as a new therapeutic target.

RAB17 and LMO4 modulate ferroptosis by regulating GPX4 expression through the Nrf2-Keap1 signaling pathway.