ETS1-mediated Regulation of SOAT1 Enhances the Malignant Phenotype of Oral Squamous Cell Carcinoma and Induces Tumor-associated Macrophages M2-like Polarization

Oral squamous cell carcinoma (OSCC) is an aggressive cancer that poses a substantial threat to human life and quality of life globally. Lipid metabolism reprogramming significantly influences tumor development, affecting not only tumor cells but also tumor-associated macrophages (TAMs) infiltration. , a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased expression enhanced the capabilities of cell proliferation, tumor sphere formation, migration, and invasion in OSCC cells, upregulated the SREBP1-regulated adipogenic pathway, activated the PI3K/AKT/mTOR pathway and promoted M2-like polarization of TAMs, thereby contributing to OSCC growth both and . Additionally, we explored the upstream transcription factors that regulate and discovered that positively regulates expression levels. Knockdown of effectively inhibited the malignant phenotype of OSCC cells, whereas restoring expression significantly mitigated this suppression. Based on these findings, we suggest that is regulated by and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that is a promising target for OSCC therapy with tremendous potential.