Abstract
Pyruvate kinase M2 (PKM2), a subtype of pyruvate kinase (PK), has been shown to play an important role in the development of cancer. It regulates the last step of glycolytic pathway. PKM2 has both pyruvate kinase and protein kinase activity, and the conversion of these two functions of PKM2 depends on the mutual change of dimer and tetramer. The dimerization of PKM2 can promote the proliferation and growth of tumor cells, so inhibiting the dimerization of PKM2 is essential to curing cancer. The aggregation of PKM2 is regulated by both endogenous and exogenous cofactors as well as post-translational modification (PTM). Although there are many studies on the different aggregation of PKM2 in the process of tumor development, there are few summaries in recent years. In this review, we first introduce the role of PKM2 in various biological processes of tumor growth. Then, we summarize the aggregation regulation mechanism of PKM2 by various endogenous cofactors such as Fructose-1, 6-diphosphate (FBP), various amino acids, and post-translational modification (PTMs). Finally, the related inhibitors and agonists of PKM2 are summarized to provide reference for regulating PKM2 aggregation in the treatment of cancer in the future.
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We would like to thank Dr. Joseph Elliot at the University of Kansas for her assistance with English language and grammatical editing of the manuscript.
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This work was supported by the National Natural Science Foundation of China (Grant No. 81930114 and 82322074), Key-Area Research and Development Program of Guangdong Province (Grant No. 2020B1111100004), the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Laboratory, Grant No. 2020B1212030006).
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The authors declare that all data were generated in-house and that no paper mill was used. Bingxin Wu, Investigation, Writing—Original Draft. **aojun Teng, Investigation. Huan Lan, Visualization. Zuhui Liang, Visualization, Investigation. Caiyan Wang, Writing—Review & Editing.
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Key Points
Compared with normal tissues, PKM2 is highly expressed in cancer cells and affects the occurrence and development of cancer cells.
The conformational changes of PKM2 affect the survival and development of cancer cells.
Targeted regulation of PKM2 conformational changes is an effective means for the treatment of cancer in the future.
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Wu, B., Liang, Z., Lan, H. et al. The role of PKM2 in cancer progression and its structural and biological basis. J Physiol Biochem 80, 261–275 (2024). https://doi.org/10.1007/s13105-024-01007-0
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DOI: https://doi.org/10.1007/s13105-024-01007-0