Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator

Tsan-Jan Chen1, Chun-Hsien Wu2, Mien-Chie Hung3

  • 1Institute of Molecular and Cellular Biology, College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan.

PubMed

Insights

Pyruvate kinase M2 (PKM2) is a key enzyme in cancer, acting in the nucleus to promote tumor growth and metastasis. Targeting nuclear PKM2 (nPKM2) offers a promising strategy for precision cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Pyruvate kinase M2 (PKM2) is a glycolytic enzyme with functions beyond metabolism.
  • PKM2's unique properties, including nuclear translocation, differentiate it from PKM1.

Purpose of the Study:

  • To review the structural basis and post-translational modifications of PKM2.
  • To explore the role of nuclear PKM2 (nPKM2) in cancer progression.
  • To discuss therapeutic strategies targeting nPKM2.

Main Methods:

  • Literature review and synthesis of current research on PKM2 structure, function, and regulation.
  • Analysis of PKM2's role in gene transcription and cellular processes.
  • Examination of emerging therapeutic approaches.

Main Results:

  • PKM2 translocates to the nucleus, where it acts as a co-transcriptional activator and protein kinase.
  • nPKM2 regulates genes involved in glycolysis, lipogenesis, redox balance, and cell cycle, reinforcing the Warburg effect.
  • nPKM2 promotes tumor growth, metastasis, and stress resistance, functioning as an oncoprotein.

Conclusions:

  • Nuclear PKM2 is a critical oncoprotein driving key aspects of cancer.
  • Targeting nPKM2, through small molecules stabilizing its tetrameric form or disrupting nuclear functions, presents a viable precision cancer therapy approach.

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