# SLC16A1 Inhibits Ferroptosis and Promotes the Progression of Head and Neck Squamous Cell Carcinoma

## TL;DR

This study shows that SLC16A1 promotes head and neck cancer growth by protecting cancer cells from a type of cell death called ferroptosis.

## Contribution

The study identifies SLC16A1 as a novel driver of HNSCC progression through ferroptosis resistance.

## Key findings

- SLC16A1 is overexpressed in HNSCC and linked to poor patient outcomes.
- SLC16A1 knockdown reduces cancer cell proliferation and increases lipid peroxidation.
- Overexpression of SLC16A1 enhances tumor growth in animal models.

## Abstract

The solute carrier family 16 member 1 (SLC16A1) gene demonstrates abnormally elevated expression levels in a variety of human malignant tumors, and it is pivotal in tumor initiation and progression. Nonetheless, the precise mechanisms through which this gene operates in head and neck squamous cell carcinoma (HNSCC) need to be elucidated. This study integrated bioinformatics analysis with clinical patient samples to elucidate that the mRNA and protein levels of SLC16A1 were significantly upregulated in patients with HNSCC, which was closely associated with poor patient prognosis. In addition, through the construction of stable SLC16A1 knockdown and overexpression models in HNSCC cells along with in vitro and in vivo experiments, the study comprehensively illuminated the pivotal role of SLC16A1 in promoting the proliferation, migration, and invasiveness of HNSCC cells, as well as enhancing their resistance to ferroptosis. In vitro experimental results demonstrated that when SLC16A1 was knocked down, the proliferation, migration, and invasion capabilities of HNSCC cell lines were significantly reduced and the extent of RAS-selective lethal 3-induced lipid peroxidation increased compared with control cells. Conversely, HNSCC cell lines overexpressing SLC16A1 exhibited enhanced proliferation, migration, and invasion capabilities, accompanied by lower levels of lipid peroxidation. In vivo experiments further corroborated the pivotal role of SLC16A1 in promoting HNSCC tumor growth. Our research findings indicate that SLC16A1 acts as an oncogene in HNSCC, and that abnormally high expression of SLC16A1 significantly accelerates the development and progression of HNSCC by conferring resistance to ferroptosis.