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Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis

Wei Gao, Yuliang Zhang, Hongjie Luo, Min Niu, Xiwang Zheng, Wanglai Hu, Jiajia Cui, Xuting Xue, Yunfeng Bo, Fengsheng Dai, Yan Lu, Dongli Yang (+14 others)
2020 Cell Death and Disease  

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https://web.archive.org/web/20210429045737/https://www.nature.com/articles/s41419-020-03104-6.pdf?error=cookies_not_supported&code=19aff204-2889-494e-bbe6-8dfa049eb930

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Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments
more » ... monstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis "SKA3-PLK1-AKT" plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.
doi:10.1038/s41419-020-03104-6 pmid:33106477 pmcid:PMC7589524 fatcat:sy45ooxq2rfi7cerlrfwroarua
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Wei Gao, Yuliang Zhang, Hongjie Luo, Min Niu, Xiwang Zheng, Wanglai Hu, Jiajia Cui, Xuting Xue, Yunfeng Bo, Fengsheng Dai, Yan Lu, Dongli Yang, Yujia Guo, Huina Guo, Huizheng Li, Yu Zhang, Tao Yang, Li Li, Linshi Zhang, Rui Hou, Shuxin Wen, Changming An, Teng Ma, Lei Jin, Wei Xu, Yongyan Wu. "Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis." Cell Death and Disease 11.10 (2020) 919