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Positioning determines function: Wandering PKM2 performs different roles in tumor cells
Shuo He1, Yan Liang1, Yiyi Tan2
1Department of Pathology, Basic Medicine College, Xinjiang Medical University, Urumqi, China.
Abstract:
Short for pyruvate kinase M2 subtype, PKM2 can be said of all-round player that is notoriously known for its metabolic involvement in glycolysis. Holding a dural role as a metabolic or non-metabolic (kinase) enzyme, PKM2 has drawn extensive attention over its biological roles implicated in tumor cells, including proliferation, migration, invasion, metabolism, and so on. wandering PKM2 can be transboundary both intracellularly and extracellularly. Specifically, PKM2 can be nuclear, cytoplasmic, mitochondrial, exosomal, or even circulate within the body. Importantly, PKM2 can function as an RNA-binding protein (RBP) to self-support its metabolic function. Despite extensive investigations or reviews available surrounding the biological roles of PKM2 from different angles in tumor cells, little has been described regarding some novel role of PKM2 that has been recently found, including, for example, acting as RNA-binding protein, protection of Golgi apparatus, and remodeling of microenvironment, and so forth. Given these findings, in this review, we summarize the recent advancements made in PKM2 research, mainly from non-metabolic respects. By the way, PKM1, another paralog of PKM2, seems to have been overlooked or under-investigated since its discovery. Some recent discoveries made about PKM1 are also preliminarily mentioned and discussed.
Insights
Pyruvate kinase M2 (PKM2) is a versatile enzyme involved in cancer cell metabolism and non-metabolic functions. This review highlights recent discoveries on PKM2
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme with dual roles as a metabolic and non-metabolic (kinase) enzyme.
- PKM2 is extensively studied for its involvement in tumor cell proliferation, migration, invasion, and metabolism.
- PKM2 exhibits dynamic localization, found intracellularly (nuclear, cytoplasmic, mitochondrial) and extracellularly (exosomal, circulating).
Purpose of the Study:
- To review recent advancements in PKM2 research, focusing on its non-metabolic functions.
- To discuss novel roles of PKM2, such as RNA-binding protein activity, Golgi apparatus protection, and microenvironment remodeling.
- To briefly introduce recent findings on PKM1, the paralog of PKM2.
Main Methods:
- Literature review of recent studies on PKM2 and PKM1.
- Synthesis of information on PKM2's diverse cellular locations and functions.
- Analysis of non-metabolic roles and emerging functions of PKM2.
Main Results:
- PKM2 functions beyond glycolysis, acting as an RNA-binding protein (RBP) to support its metabolic activity.
- Emerging roles of PKM2 include protection of the Golgi apparatus and remodeling of the tumor microenvironment.
- PKM1, a related enzyme, is under-investigated, with recent discoveries beginning to emerge.
Conclusions:
- PKM2 possesses significant non-metabolic functions crucial in cancer biology.
- Further research into PKM2's novel roles and its paralog PKM1 is warranted.
- Understanding PKM2's multifaceted roles can offer new therapeutic strategies in oncology.
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