Menin and menin-associated proteins coregulate cancer energy metabolism

Chih Wei Chou, Xi Tan, Chia Nung Hung, Brandon Lieberman, Meizhen Chen, Meena Kusi, Kohzoh Mitsuya, Chun Lin Lin, Masahiro Morita, Zhijie Liu, Chun Liang Chen, Tim Hui Ming Huang

Research output: Contribution to journalArticlepeer-review

Abstract

The interplay between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is central to maintain energy homeostasis. It remains to be determined whether there is a mechanism governing metabolic fluxes based on substrate availability in microenvironments. Here we show that menin is a key transcription factor regulating the expression of OXPHOS and glycolytic genes in cancer cells and primary tumors with poor prognosis. A group of menin-associated proteins (MAPs), including KMT2A, MED12, WAPL, and GATA3, is found to restrain menin’s full function in this transcription regulation. shRNA knockdowns of menin and MAPs result in reduced ATP production with proportional alterations of cellular energy generated through glycolysis and OXPHOS. When shRNA knockdown cells are exposed to metabolic stress, the dual functionality can clearly be distinguished among these metabolic regulators. A MAP can negatively counteract the regulatory mode of menin for OXPHOS while the same protein positively influences glycolysis. A close-proximity interaction between menin and MAPs allows transcriptional regulation for metabolic adjustment. This coordinate regulation by menin and MAPs is necessary for cells to rapidly adapt to fluctuating microenvironments and to maintain essential metabolic functions.

Original languageEnglish (US)
Article number2715
Pages (from-to)1-21
Number of pages21
JournalCancers
Volume12
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Circulating tumor cells
  • Glycolysis
  • Menin
  • Menin-associated proteins
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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