American Association for Cancer Research
00085472can204190-sup-257302_2_supp_7192352_qhrhf1.xlsx (76.5 kB)

Table S5 from Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes

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posted on 2023-03-31, 04:22 authored by Maria Apostolidi, Ioannis A. Vathiotis, Viswanathan Muthusamy, Patricia Gaule, Brandon M. Gassaway, David L. Rimm, Jesse Rinehart

CDK/cyclin gene expression analysis in TCGA BRCA database.


National Institutes of Health


National Cancer Institute




Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with low survival rate and a lack of biomarkers and targeted treatments. Here, we target pyruvate kinase M2 (PKM2), a key metabolic component of oncogenesis. In patients with TNBC, PKM2pS37 was identified as a prominent phosphoprotein corresponding to the aggressive breast cancer phenotype that showed a characteristic nuclear staining pattern and prognostic value. Phosphorylation of PKM2 at S37 was connected with a cyclin-dependent kinase (CDK) pathway in TNBC cells. In parallel, pyruvate kinase activator TEPP-46 bound PKM2pS37 and reduced its nuclear localization. In a TNBC mouse xenograft model, treatment with either TEPP-46 or the potent CDK inhibitor dinaciclib reduced tumor growth and diminished PKM2pS37. Combinations of dinaciclib with TEPP-46 reduced cell invasion, impaired redox balance, and triggered cancer cell death. Collectively, these data support an approach to identify PKM2pS37-positive TNBC and target the PKM2 regulatory axis as a potential treatment. PKM2 phosphorylation marks aggressive breast cancer cell phenotypes and targeting PKM2pS37 could be an effective therapeutic approach for treating triple-negative breast cancer.