Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway

Lingqin Yuan, Xiugui Sheng, Adam K. Willson, Dario R. Roque, Jessica E. Stine, Hui Guo, Hannah M. Jones, Chunxiao Zhou, Victoria L. Bae-Jump*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)577-591
Number of pages15
JournalEndocrine-related cancer
Volume22
Issue number4
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

Keywords

  • Glutamate dehydrogenase
  • Glutaminase
  • Ovarian cancer
  • mTOR/S6
  • siRNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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    Yuan, L., Sheng, X., Willson, A. K., Roque, D. R., Stine, J. E., Guo, H., Jones, H. M., Zhou, C., & Bae-Jump, V. L. (2015). Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway. Endocrine-related cancer, 22(4), 577-591. https://doi.org/10.1530/ERC-15-0192