PDF(Pubmed)
Abstract：
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.
摘要：
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。脂质代谢重编程显著影响肿瘤的发展，不仅影响肿瘤细胞，而且影响肿瘤相关巨噬细胞（TAMs）浸润。SOAT1是脂质代谢的关键酶，在各种癌症中具有很高的预后价值。这项研究表明，SOAT1在OSCC组织中高表达，并与M2TAMs浸润呈正相关。SOAT1表达的增加增强了细胞增殖的能力，肿瘤球的形成，迁移,和侵袭OSCC细胞，上调SREBP1调节的成脂途径，激活PI3K/AKT/mTOR通路并促进TAMs的M2样极化，从而有助于体外和体内的OSCC生长。此外,我们探索了调节SOAT1的上游转录因子，并发现ETS1正调节SOAT1的表达水平。敲低ETS1能有效抑制OSCC细胞的恶性表型,而恢复SOAT1表达可显着减轻这种抑制。基于这些发现,我们认为SOAT1受ETS1调节，通过促进脂质代谢和TAM的M2样极化在OSCC的发展中起关键作用。我们认为SOAT1是OSCC治疗的有希望的靶标，具有巨大的潜力。
