甲状腺癌(TC)是最常见的内分泌肿瘤，其中间变性甲状腺癌(ATC)最为致命。Aurora-A通常作为肿瘤基因发挥作用，其抑制剂Alisertib在各种肿瘤中具有强大的抗肿瘤作用。然而，Aurora-A在调节TC细胞能量供应方面的机制仍不清楚。在本研究中，我们证明了Alisertib的抗肿瘤作用和高Aurora-A表达与短期生存率之间的关联。多组学数据和体外验证数据表明，Aurora-A诱导PFKFB3介导的糖酵解增加ATP供应，显著上调了ERK和AKT的磷酸化。此外，Alisertib和Sorafenib的组合具有协同作用，在移植瘤模型和体外进一步确认。总的来说，我们的研究提供了Aurora-A表达的预后价值的有力证据，并表明Aurora-A上调PFKFB3介导的糖酵解，增强ATP供应，促进TC进展。将Alisertib与Sorafenib结合起来，在治疗晚期甲状腺癌方面具有巨大的应用前景。 ©2023年作者。

Thyroid cancer (TC) is the most common endocrine tumor, amongst which anaplastic thyroid carcinoma (ATC) is the most deadly. Aurora-A usually functions as oncogenes, and its inhibitor Alisertib exerts a powerful antitumor effect in various tumors. However, the mechanism of Aurora-A in regulating TC cell energy supply remains unclear. In the present study, we demonstrated the antitumor effect of Alisertib and an association between high Aurora-A expression and shorter survival. Multi-omics data and in vitro validation data suggested that Aurora-A induced PFKFB3-mediated glycolysis to increase ATP supply, which significantly upregulated the phosphorylation of ERK and AKT. Furthermore, the combination of Alisertib and Sorafenib had a synergistic effect, further confirmed in xenograft models and in vitro. Collectively, our study provides compelling evidence of the prognostic value of Aurora-A expression and suggests that Aurora-A upregulates PFKFB3-mediated glycolysis to enhance ATP supply and promote TC progression. Combining Alisertib with Sorafenib has huge prospects for application in treating advanced thyroid carcinoma.© 2023. The Author(s).