Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma

Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generat...

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Published inGenes & development Vol. 30; no. 9; pp. 1020 - 1033
Main Authors Dayton, Talya L., Gocheva, Vasilena, Miller, Kathryn M., Israelsen, William J., Bhutkar, Arjun, Clish, Clary B., Davidson, Shawn M., Luengo, Alba, Bronson, Roderick T., Jacks, Tyler, Vander Heiden, Matthew G.
Format Journal Article
LanguageEnglish
Published United States Cold Spring Harbor Laboratory Press 01.05.2016
Subjects
Animals
Carcinoma, Hepatocellular - enzymology
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - physiopathology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Proliferation - genetics
Diet, High-Fat
Embryo, Mammalian
Embryonic Development - genetics
Energy Metabolism - genetics
Female
Gene Expression Regulation, Neoplastic
Germ-Line Mutation
Growth and Development - genetics
Hepatocytes - cytology
Homeostasis - genetics
Liver Neoplasms - enzymology
Liver Neoplasms - genetics
Liver Neoplasms - physiopathology
Male
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Protein Isoforms
Research Paper
Thyroid Hormone-Binding Proteins
Thyroid Hormones - genetics
Thyroid Hormones - metabolism
PKM2
HCC
metabolism
Online AccessGet full text
ISSN0890-9369
1549-5477
DOI10.1101/gad.278549.116

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Abstract Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 -null mice ( Pkm2 −/− ). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2 −/− mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism.
AbstractList Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2-null mice (Pkm2(-/-)). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2(-/-) mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism.
Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 -null mice ( Pkm2 −/− ). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2 −/− mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism.
Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2-null mice (Pkm2 super(?/?)). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2 super(?/?) mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism.
In this study, Dayton et al. generated mice lacking PKM2, an isoform of pyruvate kinase, and found that, over time, the mice develop a metabolic syndrome that leads to spontaneous hepatocellular carcinomas (HCCs). These results provide new insights into the role of PKM2 in the regulation of systemic metabolic homeostasis and inflammation. Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to embryogenesis, tissue regeneration, and cancer. To interrogate the functional requirement for PKM2 during development and tissue homeostasis, we generated germline PKM2 -null mice ( Pkm2 −/− ). Unexpectedly, despite being the primary isoform expressed in most wild-type adult tissues, we found that Pkm2 −/− mice are viable and fertile. Thus, PKM2 is not required for embryonic or postnatal development. Loss of PKM2 leads to compensatory expression of PKM1 in the tissues that normally express PKM2. Strikingly, PKM2 loss leads to spontaneous development of hepatocellular carcinoma (HCC) with high penetrance that is accompanied by progressive changes in systemic metabolism characterized by altered systemic glucose homeostasis, inflammation, and hepatic steatosis. Therefore, in addition to its role in cancer metabolism, PKM2 plays a role in controlling systemic metabolic homeostasis and inflammation, thereby preventing HCC by a non-cell-autonomous mechanism.
Author Bhutkar, Arjun
Luengo, Alba
Jacks, Tyler
Clish, Clary B.
Gocheva, Vasilena
Miller, Kathryn M.
Dayton, Talya L.
Bronson, Roderick T.
Vander Heiden, Matthew G.
Israelsen, William J.
Davidson, Shawn M.
AuthorAffiliation 4 Metabolite Profiling Platform, Broad Institute, Cambridge, Massachusetts 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
6 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
5 Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, North Grafton, Massachusetts 01536, USA
1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
7 Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
AuthorAffiliation_xml – name: 4 Metabolite Profiling Platform, Broad Institute, Cambridge, Massachusetts 02142, USA
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– name: 2 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
– name: 5 Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, North Grafton, Massachusetts 01536, USA
– name: 6 Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
– name: 1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
– name: 3 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
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Cites_doi 10.1016/j.molcel.2011.04.025
10.1053/j.gastro.2007.04.061
10.1038/nrc1934
10.1038/nchembio.1060
10.1038/ng.3252
10.1038/nature10598
10.1073/pnas.0506580102
10.1016/j.molcel.2012.09.028
10.1016/j.cell.2012.07.018
10.1038/nmeth.1528
10.1038/ncb2629
10.1038/nature08697
10.1053/j.gastro.2003.10.065
10.1016/j.cell.2014.07.048
10.1073/pnas.0402511101
10.2337/dc12-0336
10.1016/j.cell.2011.02.013
10.1016/j.it.2014.12.008
10.1371/journal.pone.0115036
10.1093/bioinformatics/btt087
10.1016/j.molcel.2014.10.027
10.1038/nrc3162
10.1038/nrc2981
10.3748/wjg.v21.i4.1189
10.1172/JCI200420513
10.1093/bioinformatics/btp120
10.1016/j.molcel.2014.02.015
10.1016/j.tibs.2014.06.005
10.1016/j.cell.2004.11.004
10.1016/S0021-9258(18)47947-1
10.1038/nature11540
10.1016/j.molcel.2012.01.001
10.1186/1471-2105-12-323
10.1038/nrc4017
10.3810/pgm.2009.11.2074
10.1111/j.1432-1033.1996.00366.x
10.1016/j.gde.2009.01.002
10.1016/j.semcancer.2005.04.009
10.1038/nature06667
10.1126/science.1140485
10.1073/pnas.0914845107
10.1016/j.jhep.2011.10.027
10.1016/j.molcel.2015.07.013
10.1016/j.gene.2013.12.062
10.1016/j.cell.2011.03.054
10.1016/j.cell.2014.05.051
10.1038/nature06734
10.1016/j.jhep.2014.12.012
10.1016/j.biocel.2010.02.005
10.1126/scisignal.2000431
10.1016/j.cmet.2011.08.005
10.1038/nature11247
10.1371/journal.pone.0031812
10.1126/science.1188015
10.1158/0008-5472.CAN-14-2371
10.1126/science.1218595
10.1073/pnas.93.12.5860
10.1016/j.cell.2013.09.025
10.1093/carcin/19.1.99
10.4251/wjgo.v5.i9.186
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Issue 9
Keywords PKM2
HCC
metabolism
Language English
License 2016 Dayton et al.; Published by Cold Spring Harbor Laboratory Press.
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References 2021111619520344000_30.9.1020.48
2021111619520344000_30.9.1020.49
2021111619520344000_30.9.1020.40
2021111619520344000_30.9.1020.41
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(2021111619520344000_30.9.1020.43) 1987; 262
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(2021111619520344000_30.9.1020.17) 2011; 11
2021111619520344000_30.9.1020.62
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2021111619520344000_30.9.1020.24
(2021111619520344000_30.9.1020.34) 2012; 31
2021111619520344000_30.9.1020.25
2021111619520344000_30.9.1020.9
2021111619520344000_30.9.1020.8
(2021111619520344000_30.9.1020.26) 2014; 2014
2021111619520344000_30.9.1020.7
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2021111619520344000_30.9.1020.5
2021111619520344000_30.9.1020.4
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2021111619520344000_30.9.1020.18
2021111619520344000_30.9.1020.19
(2021111619520344000_30.9.1020.50) 1996; 235
2021111619520344000_30.9.1020.51
2021111619520344000_30.9.1020.52
2021111619520344000_30.9.1020.53
2021111619520344000_30.9.1020.10
2021111619520344000_30.9.1020.54
2021111619520344000_30.9.1020.11
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2021111619520344000_30.9.1020.56
2021111619520344000_30.9.1020.13
2021111619520344000_30.9.1020.57
2021111619520344000_30.9.1020.14
2021111619520344000_30.9.1020.58
2021111619520344000_30.9.1020.60
2021111619520344000_30.9.1020.61
References_xml – ident: 2021111619520344000_30.9.1020.37
  doi: 10.1016/j.molcel.2011.04.025
– ident: 2021111619520344000_30.9.1020.11
  doi: 10.1053/j.gastro.2007.04.061
– ident: 2021111619520344000_30.9.1020.15
  doi: 10.1038/nrc1934
– ident: 2021111619520344000_30.9.1020.1
  doi: 10.1038/nchembio.1060
– ident: 2021111619520344000_30.9.1020.48
  doi: 10.1038/ng.3252
– ident: 2021111619520344000_30.9.1020.58
  doi: 10.1038/nature10598
– ident: 2021111619520344000_30.9.1020.49
  doi: 10.1073/pnas.0506580102
– ident: 2021111619520344000_30.9.1020.59
  doi: 10.1016/j.molcel.2012.09.028
– ident: 2021111619520344000_30.9.1020.60
  doi: 10.1016/j.cell.2012.07.018
– ident: 2021111619520344000_30.9.1020.25
  doi: 10.1038/nmeth.1528
– ident: 2021111619520344000_30.9.1020.61
  doi: 10.1038/ncb2629
– ident: 2021111619520344000_30.9.1020.10
  doi: 10.1038/nature08697
– ident: 2021111619520344000_30.9.1020.12
  doi: 10.1053/j.gastro.2003.10.065
– ident: 2021111619520344000_30.9.1020.56
  doi: 10.1016/j.cell.2014.07.048
– ident: 2021111619520344000_30.9.1020.54
  doi: 10.1073/pnas.0402511101
– ident: 2021111619520344000_30.9.1020.14
  doi: 10.2337/dc12-0336
– ident: 2021111619520344000_30.9.1020.19
  doi: 10.1016/j.cell.2011.02.013
– ident: 2021111619520344000_30.9.1020.39
  doi: 10.1016/j.it.2014.12.008
– volume: 2014
  start-page: 943162
  year: 2014
  ident: 2021111619520344000_30.9.1020.26
  article-title: A comprehensive review on metabolic syndrome
  publication-title: Cardiol Res Pract
– ident: 2021111619520344000_30.9.1020.57
  doi: 10.1371/journal.pone.0115036
– ident: 2021111619520344000_30.9.1020.30
  doi: 10.1093/bioinformatics/btt087
– ident: 2021111619520344000_30.9.1020.35
  doi: 10.1016/j.molcel.2014.10.027
– volume: 11
  start-page: 835
  year: 2011
  ident: 2021111619520344000_30.9.1020.17
  article-title: Choline metabolism in malignant transformation
  publication-title: Nat Rev Cancer
  doi: 10.1038/nrc3162
– ident: 2021111619520344000_30.9.1020.5
  doi: 10.1038/nrc2981
– ident: 2021111619520344000_30.9.1020.31
  doi: 10.3748/wjg.v21.i4.1189
– ident: 2021111619520344000_30.9.1020.21
  doi: 10.1172/JCI200420513
– ident: 2021111619520344000_30.9.1020.52
  doi: 10.1093/bioinformatics/btp120
– ident: 2021111619520344000_30.9.1020.27
  doi: 10.1016/j.molcel.2014.02.015
– ident: 2021111619520344000_30.9.1020.45
  doi: 10.1016/j.tibs.2014.06.005
– ident: 2021111619520344000_30.9.1020.44
  doi: 10.1016/j.cell.2004.11.004
– volume: 262
  start-page: 14366
  year: 1987
  ident: 2021111619520344000_30.9.1020.43
  article-title: The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters
  publication-title: J Biol Chem
  doi: 10.1016/S0021-9258(18)47947-1
– ident: 2021111619520344000_30.9.1020.6
  doi: 10.1038/nature11540
– ident: 2021111619520344000_30.9.1020.16
  doi: 10.1016/j.molcel.2012.01.001
– ident: 2021111619520344000_30.9.1020.32
  doi: 10.1186/1471-2105-12-323
– ident: 2021111619520344000_30.9.1020.38
  doi: 10.1038/nrc4017
– ident: 2021111619520344000_30.9.1020.46
  doi: 10.3810/pgm.2009.11.2074
– volume: 235
  start-page: 366
  year: 1996
  ident: 2021111619520344000_30.9.1020.50
  article-title: Alternative splicing of the pyruvate kinase M gene in a minigene system
  publication-title: Eur J Biochem
  doi: 10.1111/j.1432-1033.1996.00366.x
– ident: 2021111619520344000_30.9.1020.51
  doi: 10.1016/j.gde.2009.01.002
– ident: 2021111619520344000_30.9.1020.41
  doi: 10.1016/j.semcancer.2005.04.009
– ident: 2021111619520344000_30.9.1020.8
  doi: 10.1038/nature06667
– ident: 2021111619520344000_30.9.1020.42
  doi: 10.1126/science.1140485
– ident: 2021111619520344000_30.9.1020.9
  doi: 10.1073/pnas.0914845107
– ident: 2021111619520344000_30.9.1020.2
  doi: 10.1016/j.jhep.2011.10.027
– ident: 2021111619520344000_30.9.1020.22
  doi: 10.1016/j.molcel.2015.07.013
– volume: 31
  start-page: 5
  year: 2012
  ident: 2021111619520344000_30.9.1020.34
  article-title: Nonmetabolic functions of pyruvate kinase isoform M2 in controlling cell cycle progression and tumorigenesis
  publication-title: Chin J Cancer
– ident: 2021111619520344000_30.9.1020.62
  doi: 10.1016/j.gene.2013.12.062
– ident: 2021111619520344000_30.9.1020.36
  doi: 10.1016/j.cell.2011.03.054
– ident: 2021111619520344000_30.9.1020.53
  doi: 10.1016/j.cell.2014.05.051
– ident: 2021111619520344000_30.9.1020.7
  doi: 10.1038/nature06734
– ident: 2021111619520344000_30.9.1020.4
  doi: 10.1016/j.jhep.2014.12.012
– ident: 2021111619520344000_30.9.1020.40
  doi: 10.1016/j.biocel.2010.02.005
– ident: 2021111619520344000_30.9.1020.20
  doi: 10.1126/scisignal.2000431
– ident: 2021111619520344000_30.9.1020.3
  doi: 10.1016/j.cmet.2011.08.005
– ident: 2021111619520344000_30.9.1020.13
  doi: 10.1038/nature11247
– ident: 2021111619520344000_30.9.1020.28
  doi: 10.1371/journal.pone.0031812
– ident: 2021111619520344000_30.9.1020.55
  doi: 10.1126/science.1188015
– ident: 2021111619520344000_30.9.1020.33
  doi: 10.1158/0008-5472.CAN-14-2371
– ident: 2021111619520344000_30.9.1020.24
  doi: 10.1126/science.1218595
– ident: 2021111619520344000_30.9.1020.29
  doi: 10.1073/pnas.93.12.5860
– ident: 2021111619520344000_30.9.1020.23
  doi: 10.1016/j.cell.2013.09.025
– ident: 2021111619520344000_30.9.1020.18
  doi: 10.1093/carcin/19.1.99
– ident: 2021111619520344000_30.9.1020.47
  doi: 10.4251/wjgo.v5.i9.186
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Snippet Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to...
Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of pyruvate kinase (PK), and PKM2 expression is closely linked to...
In this study, Dayton et al. generated mice lacking PKM2, an isoform of pyruvate kinase, and found that, over time, the mice develop a metabolic syndrome that...
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StartPage 1020
SubjectTerms Animals
Carcinoma, Hepatocellular - enzymology
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - physiopathology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Proliferation - genetics
Diet, High-Fat
Embryo, Mammalian
Embryonic Development - genetics
Energy Metabolism - genetics
Female
Gene Expression Regulation, Neoplastic
Germ-Line Mutation
Growth and Development - genetics
Hepatocytes - cytology
Homeostasis - genetics
Liver Neoplasms - enzymology
Liver Neoplasms - genetics
Liver Neoplasms - physiopathology
Male
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Protein Isoforms
Research Paper
Thyroid Hormone-Binding Proteins
Thyroid Hormones - genetics
Thyroid Hormones - metabolism
Title Germline loss of PKM2 promotes metabolic distress and hepatocellular carcinoma
URI https://www.ncbi.nlm.nih.gov/pubmed/27125672
https://www.proquest.com/docview/1787480775
https://www.proquest.com/docview/1790947488
https://pubmed.ncbi.nlm.nih.gov/PMC4863734
Volume 30
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