2. Academic Validation
  3. Targeting Aurora-A inhibits tumor progression and sensitizes thyroid carcinoma to Sorafenib by decreasing PFKFB3-mediated glycolysis

Targeting Aurora-A inhibits tumor progression and sensitizes thyroid carcinoma to Sorafenib by decreasing PFKFB3-mediated glycolysis

  • Cell Death Dis. 2023 Mar 29;14(3):224. doi: 10.1038/s41419-023-05709-z.
Zhi Jingtai # 1 2,  Hu Linfei # 1,  Qian Yuyang # 3,  Kang Ning 1,  Yun Xinwei 1,  Wang Xin 1,  Ruan Xianhui 1,  Huang Dongmei 1,  Yang Weiwei 2,  Meng Xiangrui 1,  Zhu Tianze 4,  Wang Wei 5,  Zheng Xiangqian 6
Affiliations

Affiliations

  • 1 Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
  • 2 Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Rehabilitation Road No.24, 300192, Tianjin, People's Republic of China.
  • 3 State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, 300071, Tianjin, China.
  • 4 Department of Clinical Medicine, The Clinical Medicine of Tianjin Medical University, 300070, Tianjin, People's Republic of China.
  • 5 Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin First Central Hospital, Institute of Otolaryngology of Tianjin, Key Laboratory of Auditory Speech and Balance Medicine, Key Medical Discipline of Tianjin (Otolaryngology), Quality Control Centre of Otolaryngology, Rehabilitation Road No.24, 300192, Tianjin, People's Republic of China. wwei1106@hotmail.com.
  • 6 Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China. xzheng05@tmu.edu.cn.
  • # Contributed equally.
PMID: 36990998 DOI: 10.1038/s41419-023-05709-z
Abstract

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.

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