Pyruvate kinase M1 regulates butyrate metabolism in cancerous colonocytes.

Butyrates / metabolism Colorectal Neoplasms / enzymology Glycolysis Humans Isoenzymes Pyruvate Kinase / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 05 2022
Historique:
received: 19 11 2021
accepted: 05 05 2022
entrez: 24 5 2022
pubmed: 25 5 2022
medline: 27 5 2022
Statut: epublish

Résumé

Colorectal cancer (CRC) cells shift metabolism toward aerobic glycolysis and away from using oxidative substrates such as butyrate. Pyruvate kinase M1/2 (PKM) is an enzyme that catalyzes the last step in glycolysis, which converts phosphoenolpyruvate to pyruvate. M1 and M2 are alternatively spliced isoforms of the Pkm gene. The PKM1 isoform promotes oxidative metabolism, whereas PKM2 enhances aerobic glycolysis. We hypothesize that the PKM isoforms are involved in the shift away from butyrate oxidation towards glycolysis in CRC cells. Here, we find that PKM2 is increased and PKM1 is decreased in human colorectal carcinomas as compared to non-cancerous tissue. To test whether PKM1/2 alter colonocyte metabolism, we created a knockdown of PKM2 and PKM1 in CRC cells to analyze how butyrate oxidation and glycolysis would be impacted. We report that butyrate oxidation in CRC cells is regulated by PKM1 levels, not PKM2. Decreased butyrate oxidation observed through knockdown of PKM1 and PKM2 is rescued through re-addition of PKM1. Diminished PKM1 lowered mitochondrial basal respiration and decreased mitochondrial spare capacity. We demonstrate that PKM1 suppresses glycolysis and inhibits hypoxia-inducible factor-1 alpha. These data suggest that reduced PKM1 is, in part, responsible for increased glycolysis and diminished butyrate oxidation in CRC cells.

Identifiants

DOI: 10.1038/s41598-022-12827-9 PMID: 35610475 PMC: PMC9130307
pubmed: 35610475
doi: 10.1038/s41598-022-12827-9
pii: 10.1038/s41598-022-12827-9
pmc: PMC9130307
doi:

Substances chimiques

Butyrates 0
Isoenzymes 0
Pyruvate Kinase EC 2.7.1.40

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

8771

Subventions

Organisme : NIDDK NIH HHS
ID : R00 DK100736
Pays : United States

Informations de copyright

© 2022. The Author(s).

Références

Curr Pharm Biotechnol. 2008 Dec;9(6):510-5
pubmed: 19075689
J Biol Chem. 2017 Sep 15;292(37):15561-15576
pubmed: 28778925
Mol Cancer. 2012 Oct 09;11:76
pubmed: 23043612
Aging (Albany NY). 2021 Jan 20;13(4):5034-5054
pubmed: 33495406
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Structure. 1998 Feb 15;6(2):195-210
pubmed: 9519410
J Nutr. 1991 Jun;121(6):869-78
pubmed: 1903440
Oncogenesis. 2014 Jan 13;3:e84
pubmed: 24418892
J Cell Physiol. 2009 Jan;218(1):58-65
pubmed: 18767040
CA Cancer J Clin. 2020 May;70(3):145-164
pubmed: 32133645
Semin Cell Dev Biol. 2020 Feb;98:63-70
pubmed: 31129171
Oncol Rep. 2008 Jan;19(1):81-91
pubmed: 18097579
Cancer Metab. 2017 Nov 30;5:10
pubmed: 29214019
IUBMB Life. 2012 Sep;64(9):775-82
pubmed: 22807066
Nature. 2008 Mar 13;452(7184):230-3
pubmed: 18337823
Anal Chem. 2009 Aug 15;81(16):6868-78
pubmed: 19555051
Nature. 2008 Mar 13;452(7184):181-6
pubmed: 18337815
Cancer Cell. 2018 Mar 12;33(3):355-367.e7
pubmed: 29533781
Sci Rep. 2019 Apr 17;9(1):6212
pubmed: 30996297
Oncotarget. 2013 Feb;4(2):182-3
pubmed: 23563701
Lab Invest. 2017 Aug;97(8):962-970
pubmed: 28414323
Oncogene. 2016 Apr 21;35(16):2031-9
pubmed: 26234680
Adv Cancer Res. 2017;135:119-149
pubmed: 28882220
Int J Clin Exp Pathol. 2015 Sep 01;8(9):11393-9
pubmed: 26617865
Sci Rep. 2015 Feb 27;5:8647
pubmed: 25721733
Mol Cell. 2012 Nov 30;48(4):612-26
pubmed: 23063526
Cancer Res. 2006 Feb 1;66(3):1684-936
pubmed: 16452228
Cancer Lett. 2019 May 1;449:31-44
pubmed: 30742945
Oncol Rep. 2012 Oct;28(4):1346-52
pubmed: 22895557
Cancer Sci. 2021 Jan;112(1):41-50
pubmed: 33070451
Cancer Lett. 2015 Jul 10;363(1):17-27
pubmed: 25818238
Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19
pubmed: 17973645
Oncotarget. 2016 Apr 5;7(14):18940-52
pubmed: 26980745
J Pediatr. 1995 Jun;126(6):910-5
pubmed: 7776094
Cancer Sci. 2016 Dec;107(12):1767-1775
pubmed: 27696637
Cell Metab. 2011 May 4;13(5):517-26
pubmed: 21531334
Gastroenterology. 1982 Aug;83(2):424-9
pubmed: 7084619
J Cancer Res Clin Oncol. 1998;124(6):315-20
pubmed: 9692838
Oncotarget. 2017 Mar 28;8(13):20543-20557
pubmed: 28423551

Auteurs

Bohye Park (B)

Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave., Knoxville, TN, 37996, USA.

Ji Yeon Kim (JY)

Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave., Knoxville, TN, 37996, USA.

Olivia F Riffey (OF)

Department of Microbiology, University of Tennessee, Knoxville, TN, 37996, USA.

Presley Dowker-Key (P)

Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave., Knoxville, TN, 37996, USA.

Antje Bruckbauer (A)

University of Tennessee Medical Center Biorepository, Knoxville, TN, 37920, USA.

James McLoughlin (J)

University of Tennessee Medical Center Biorepository, Knoxville, TN, 37920, USA.

Ahmed Bettaieb (A)

Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave., Knoxville, TN, 37996, USA.
Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN, 37996, USA.
Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, TN, 37996, USA.

Dallas R Donohoe (DR)

Department of Nutrition, University of Tennessee, 1215 W. Cumberland Ave., Knoxville, TN, 37996, USA. ddonohoe@utk.edu.
Department of Microbiology, University of Tennessee, Knoxville, TN, 37996, USA. ddonohoe@utk.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Lipides › Acides gras › Acides gras volatils › Butyrates › Pyruvate kinase M1 regulates butyrate...
Recherchemedicale.com › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › Pyruvate kinase M1 regulates butyrate...
Recherchemedicale.com › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Pyruvate kinase M1 regulates butyrate...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Pyruvate kinase M1 regulates butyrate...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Isoformes de protéines › Isoenzymes › Pyruvate kinase M1 regulates butyrate...
Recherchemedicale.com › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Pyruvate kinase › Pyruvate kinase M1 regulates butyrate...