Tyrosine Phosphorylation of Mitochondrial Creatine Kinase 1 Enhances a Druggable Tumor Energy Shuttle Pathway

Kiran Kurmi, Sadae Hitosugi, Jia Yu, Felix Boakye-Agyeman, Elizabeth K. Wiese, Thomas R. Larson, Qing Dai, Yuichi J. Machida, Zhenkun Lou, Liewei Wang, Judy C. Boughey, Scott H. Kaufmann, Matthew P. Goetz, Larry M. Karnitz, Taro Hitosugi

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Kurmi et al. report that the phosphocreatine (PCr) energy shuttle is important for breast tumor metabolism and growth. This energy shuttle is activated through MtCK1 Y153 phosphorylation by the HER2/ABL signaling axis. Using a creatine analog cyclocreatine that inhibits the PCr energy shuttle, they demonstrate reduced growth of trastuzumab-resistant breast tumors in mice.

Original languageEnglish (US)
Pages (from-to)833-847.e8
JournalCell Metabolism
Volume28
Issue number6
DOIs
StatePublished - Dec 4 2018

Keywords

  • ABL kinase
  • HER2 tyrosine kinase
  • breast cancer
  • cyclocreatine
  • mitochondria
  • mitochondrial bioenergetics
  • mitochondrial creatine kinase
  • oncogenic tyrosine kinase
  • phosphocreatine
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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