Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer

Kei Kudo, Miyuki Nomura, Yoshimi Sakamoto, Shigemi Ito, Mami Morita, Masaaki Kawai, Yoji Yamashita, Kiyoshi Ito, Hidekazu Yamada, Hiroshi Shima, Nobuo Yaegashi, Nobuhiro Tanuma

Research output: Contribution to journalArticle

Abstract

It is of current interest to target cancer metabolism as treatment for many malignancies, including ovarian cancer (OVC), in which few druggable driver mutations have been identified. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD salvage pathway, is a potential therapeutic target in OVC. However, factors that determine responsiveness to NAMPT inhibition are not fully understood. Here, we report that OVC cell lines can be divided into subgroups exhibiting NAMPT-dependent or NAMPT-independent glycolysis, and these metabolic differences correlate with vulnerability to NAMPT inhibition. Interestingly, cells showing NAMPT-dependent glycolysis were enriched in a group of cells lacking BRCA1/2 gene mutations. Our findings suggest the importance of selecting appropriate patients for NAMPT-targeting therapy in OVC.

Original languageEnglish
Pages (from-to)1379-1388
Number of pages10
JournalFEBS Letters
Volume594
Issue number9
DOIs
Publication statusPublished - 2020 May 1

Keywords

  • BRCA
  • NAD
  • NAMPT
  • cancer metabolism
  • metabolism
  • ovarian cancer

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Kudo, K., Nomura, M., Sakamoto, Y., Ito, S., Morita, M., Kawai, M., Yamashita, Y., Ito, K., Yamada, H., Shima, H., Yaegashi, N., & Tanuma, N. (2020). Divergent metabolic responses dictate vulnerability to NAMPT inhibition in ovarian cancer. FEBS Letters, 594(9), 1379-1388. https://doi.org/10.1002/1873-3468.13736