口腔鳞状细胞癌（OSCC）是一种侵袭性癌症，对全球人类生命和生活质量构成重大威胁。脂质代谢重编程显着影响肿瘤的发展，不仅影响肿瘤细胞，还影响肿瘤相关巨噬细胞（TAM）的浸润。 SOAT1 是脂质代谢中的关键酶，在多种癌症中具有很高的预后价值。本研究表明 SOAT1 在 OSCC 组织中高表达，并与 M2 TAM 浸润呈正相关。 SOAT1表达增加增强了OSCC细胞的细胞增殖、肿瘤球形成、迁移和侵袭的能力，上调SREBP1调节的脂肪生成途径，激活PI3K/AKT/mTOR途径并促进TAM的M2样极化，从而有助于OSCC 在体外和体内的生长。此外，我们探索了调节 SOAT1 的上游转录因子，发现 ETS1 正向调节 SOAT1 表达水平。 ETS1 的敲低有效抑制了 OSCC 细胞的恶性表型，而恢复 SOAT1 表达则显着减轻了这种抑制。基于这些发现，我们认为 SOAT1 受 ETS1 调节，并通过促进脂质代谢和 TAM 的 M2 样极化，在 OSCC 的发展中发挥关键作用。我们认为 SOAT1 是 OSCC 治疗的一个有前途的靶点，具有巨大的潜力。© 作者。

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. SOAT1, a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that SOAT1 is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased SOAT1 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 in vitro and in vivo. Additionally, we explored the upstream transcription factors that regulate SOAT1 and discovered that ETS1 positively regulates SOAT1 expression levels. Knockdown of ETS1 effectively inhibited the malignant phenotype of OSCC cells, whereas restoring SOAT1 expression significantly mitigated this suppression. Based on these findings, we suggest that SOAT1 is regulated by ETS1 and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that SOAT1 is a promising target for OSCC therapy with tremendous potential.© The author(s).