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Mol Cells. 2019 Sep 30;42(9):628-636. doi: 10.14348/molcells.2019.0038.

Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-kB Activity in Triple-Negative Breast Cancer Cells.

Ma C1,2, Zu X3,4,2, Liu K3,4,5,6, Bode AM7, Dong Z7, Liu Z1, Kim DJ3,4,5.

Author information

1
Department of Breast Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450008, China.
2
These authors contributed equally to this work.
3
China-US (Henan) Hormel Cancer Institute, Zhengzhou 450008, China.
4
The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450008, China.
5
The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou 450008, China.
6
International Joint Research Center of Cancer Chemoprevention, Zhengzhou 450008, China.
7
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.

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-kB (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-kB target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

KEYWORDS:

NF-kB; PKM1; PKM2; cell cycle; triple-negative breast cancer cells

PMID:
31564074
DOI:
10.14348/molcells.2019.0038
Free PMC Article

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