Isoform-specific deletion of PKM2 constrains tumor initiation in a mouse model of soft tissue sarcoma
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Author(s)
Dayton, Talya L.
Miller, Kathryn M.
Bronson, Roderick T.
Dayton, Talya L.
Gocheva, Vasilena
Miller, Kathryn
Bhutkar, Arjun
Chidley, Caroline
Vander Heiden, Matthew G.
Jacks, Tyler E.
Date Issued
May 2018
Journal
Cancer & Metabolism
Publisher
BioMed Central Ltd.
Citation
Dayton, Talya L. et al. "Isoform-specific deletion of PKM2 constrains tumor initiation in a mouse model of soft tissue sarcoma." Cancer & Metabolism 2018, 6 (May 2018): 6 © 2018 The Author(s)
Version
Final published version
Abstract
Background
Alternative splicing of the Pkm gene product generates the PKM1 and PKM2 isoforms of the glycolytic enzyme pyruvate kinase. PKM2 expression is associated with embryogenesis, tissue regeneration, and cancer. PKM2 is also the pyruvate kinase isoform expressed in most wild-type adult tissues, with PKM1 restricted primarily to skeletal muscle, heart, and brain. To interrogate the functional requirement for PKM2 during tumor initiation in an autochthonous mouse model for soft tissue sarcoma (STS), we used a conditional Pkm2 allele (Pkm2[superscript fl]) to abolish PKM2 expression.
Results
PKM2 deletion slowed tumor onset but did not abrogate eventual tumor outgrowth. PKM2-null sarcoma cells expressed PKM1 with tumors containing a high number of infiltrating PKM2 expressing stromal cells. End-stage PKM2-null tumors showed increased proliferation compared to tumors with a wild-type Pkm2 allele, and tumor metabolite analysis revealed metabolic changes associated with PKM2 loss.
Conclusions
While PKM2 is not required for soft tissue sarcoma growth, PKM2 expression may facilitate initiation of this tumor type. Because these data differ from what has been observed in other cancer models where PKM2 has been deleted, they argue that the consequences of PKM2 loss during tumor initiation are dependent on the tumor type. Keywords: PKM2; Soft tissue sarcoma;Cancer
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1186/s40170-018-0179-2
