PT  - JOURNAL ARTICLE
AU  - Liu, Shengzhi
AU  - Cai, Jin
AU  - Qian, Xiaoyu
AU  - Zhang, Junjiao
AU  - Zhang, Yi
AU  - Meng, Xiang
AU  - Wang, Mingjie
AU  - Gao, Ping
AU  - Zhong, Xiuying
TI  - TPX2 lactylation is required for the cell cycle regulation and hepatocellular carcinoma progression
AID  - 10.26508/lsa.202402978
DP  - 2025 Jun 01
TA  - Life Science Alliance
PG  - e202402978
VI  - 8
IP  - 6
4099  - http://www.life-science-alliance.org/content/8/6/e202402978.short
4100  - http://www.life-science-alliance.org/content/8/6/e202402978.full
SO  - Life Sci. Alliance2025 Jun 01; 8
AB  - Targeting protein for Xklp2 (TPX2) is critical for mitosis and spindle assembly because of its control of Aurora kinase A (AURKA). However, the regulation of TPX2 activity and its subsequent effects on mitosis and cancer progression remain unclear. Here, we show that TPX2 is lactylated at K249 in hepatocellular carcinoma (HCC) tumour tissues and that this process is regulated by the lactylase CBP and the delactylase HDAC1. Lactate reduction via either shRNAs targeting lactate dehydrogenase A or the lactate dehydrogenase A inhibitor GSK2837808A decreases the level of TPX2 lactylation. Importantly, TPX2 lactylation is required for the cell cycle regulation and tumour growth. Mechanistically, TPX2 lactylation disrupts protein phosphatase 1 (PP1) binding to AURKA, enhances AURKA T288 phosphorylation, and facilitates the cell cycle progression. Overall, our study reveals a previously unappreciated role of TPX2 lactylation in regulating cell cycle progression and HCC tumorigenesis, exposing an important correlation between metabolic reprogramming and cell cycle regulation in HCC.The previously published lactylome data of the HCC cohort reanalysed in this study were available in the NODE database (The National Omics Data Encyclopedia) with the accession code OEP002852. All other data generated or analysed in this study and source data are available upon request.