Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells

  • Ma, Chaobing (Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University) ;
  • Zu, Xueyin (China-US (Henan) Hormel Cancer Institute) ;
  • Liu, Kangdong (China-US (Henan) Hormel Cancer Institute) ;
  • Bode, Ann M. (The Hormel Institute, University of Minnesota) ;
  • Dong, Zigang (The Hormel Institute, University of Minnesota) ;
  • Liu, Zhenzhen (Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University) ;
  • Kim, Dong Joon (China-US (Henan) Hormel Cancer Institute)
  • Received : 2019.03.04
  • Accepted : 2019.08.05
  • Published : 2019.09.30
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Abstract

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

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References

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