PKM2 is not required for colon cancer initiated by APC loss
Lau, Allison N.
Israelsen, William J.
Sinnamon, Mark J.
Dayton, Talya L.
Hillis, Alissandra L.
Di Vizio, Dolores
Hung, Kenneth E.
Vander Heiden, Matthew G.Note: Order does not necessarily reflect citation order of authors.
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CitationLau, A. N., W. J. Israelsen, J. Roper, M. J. Sinnamon, L. Georgeon, T. L. Dayton, A. L. Hillis, et al. 2017. “PKM2 is not required for colon cancer initiated by APC loss.” Cancer & Metabolism 5 (1): 10. doi:10.1186/s40170-017-0172-1. http://dx.doi.org/10.1186/s40170-017-0172-1.
AbstractBackground: Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been reported to be essential in other tumor contexts, including a proposed non-metabolic role in β-catenin nuclear translocation. PKM2 is expressed in colon cancers where loss of the Apc tumor suppressor results in β-catenin nuclear translocation and aberrant activation of the canonical Wnt signaling pathway. Whether PKM2 is required in this colon cancer context has not been investigated. Results: Colon tumorigenesis was induced in mice harboring conditional Apc and Pkm2 alleles, and tumor progression was monitored by serial colonoscopy. PKM2 deletion had no effect on overall survival, the number of mice that developed tumors, or the number of tumors that developed per animal. Immunohistochemical analysis demonstrated PKM2 expression in wild-type tumors and the expected loss of PKM2 expression in tumors from Pkm2 conditional mice. Loss of PKM2 resulted in pyruvate kinase M1 expression but had no effect on nuclear β-catenin staining. These findings are consistent with tumor growth and activated Wnt signaling despite PKM2 loss in this model. We also found a large fraction of human colon cancers had very low or undetectable levels of PKM2 expression. Conclusions: PKM2 is not required for Apc-deficient colon cancer or for nuclear translocation of β-catenin in Apc-null tumor cells. These findings suggest that PKM2 expression is not required for colon tumor formation or progression. Electronic supplementary material The online version of this article (10.1186/s40170-017-0172-1) contains supplementary material, which is available to authorized users.
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