脊索瘤是一种常见的具有强侵袭性的恶性脊柱肿瘤，严重影响患者生存质量，但迄今尚缺乏明确的发病机制及治疗靶点。本项目组前期利用单细胞测序技术发现，一种调控骨代谢的转录因子Osterix在脊索瘤细胞中分布显著，并且高表达Osterix的脊索瘤患者预后较差。我们还发现，干扰Osterix表达可显著抑制脊索瘤细胞增殖、周期、侵袭迁移，而自噬现象增加。此外，Brachyury、Galectin-3、Survivin等脊索瘤相关肿瘤因子的表达也受到不同程度抑制。因此，我们初步认为Osterix作为转录因子在脊索瘤恶性生物学行为中发挥重要作用。在此基础上，本项目拟从分子、细胞水平进一步探索Osterix调控脊索瘤恶性生物学表现的作用机制，构建脊索瘤荷瘤和肺转移模型，从体内水平验证Osterix对脊索瘤增殖和转移的影响，以揭示其在脊索瘤恶性生物学行为中的关键作用，为脊索瘤的治疗提供新的理论基础和药物靶点。

Chordoma, which seriously affects the quality of life of patients, is a common malignant spinal tumor with strong invasiveness, but so far there is no clear pathogenesis and treatment targets. Using single cell sequencing technique, we found that Osterix, a transcription factor related to bone metabolism, was significantly distributed in chordoma cell subsets, and the prognosis of chordoma patients with high expression of Osterix was poor. We further found that Osterix knockdown significantly inhibited chordoma cell proliferation, migration, invasion and induced G1 phase arrest. In addition, Brachyury, Galectin-3, Survivin and other chordoma-related tumor factors were also inhibited after Osterix knockdown. Therefore, we preliminarily believe that Osterix, as an upstream transcription factor, plays an important role in the malignant behavior of chordoma. On this basis, our project intends to further explore the mechanism of Osterix in regulating the biological function of chordoma at the molecular and cellular levels. The effects of Osterix on the proliferation and metastasis of chordoma are verified in situ and metastatic tumor models, so as to reveal its key role in malignant biological behavior of chordoma and provide new theoretical basis and potential drug targets for the treatment of chordoma.