Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis
Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PK...
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| Veröffentlicht in: | Frontiers in oncology Jg. 10; S. 159 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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Frontiers Media S.A
02.03.2020
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| ISSN: | 2234-943X, 2234-943X |
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| Abstract | Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment. |
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| AbstractList | Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment. Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment.Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment. |
| Author | Ashish Mishra, Surendra Pratap Pandey, Uma Zahra, Kulsoom Dey, Tulika |
| AuthorAffiliation | 2 Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India 1 Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India 3 Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India |
| AuthorAffiliation_xml | – name: 1 Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India – name: 2 Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India – name: 3 Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University , Varanasi , India |
| Author_xml | – sequence: 1 givenname: Kulsoom surname: Zahra fullname: Zahra, Kulsoom – sequence: 2 givenname: Tulika surname: Dey fullname: Dey, Tulika – sequence: 3 surname: Ashish fullname: Ashish – sequence: 4 givenname: Surendra Pratap surname: Mishra fullname: Mishra, Surendra Pratap – sequence: 5 givenname: Uma surname: Pandey fullname: Pandey, Uma |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32195169$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2020 Zahra, Dey, Ashish, Mishra and Pandey. Copyright © 2020 Zahra, Dey, Ashish, Mishra and Pandey. 2020 Zahra, Dey, Ashish, Mishra and Pandey |
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| Keywords | cancer metabolism anaerobic glycolysis chemotherapy angiogenesis pyruvate kinase M2 |
| Language | English |
| License | Copyright © 2020 Zahra, Dey, Ashish, Mishra and Pandey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Title | Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis |
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