G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

Magdalena Dragan, Mai Uyen Nguyen, Stephania Guzman, Cameron Goertzen, Muriel Brackstone, Waljit S. Dhillo, Paul R. Bech, Sophie Clarke, Ali Abbara, Alan B. Tuck, David A. Hess, Sharon R. Pine, Wei Xing Zong, Frederic E. Wondisford, Xiaoyang Su, Andy V. Babwah, Moshmi Bhattacharya

Research output: Contribution to journalArticle

Abstract

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC.

Original languageEnglish (US)
Article number106
JournalCell Death and Disease
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2020

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All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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